cord-000128-t74b5j2j	2008	In this review, we will concentrate on peptide-mediated delivery of siRNAs and steric block oligonucleotides and discuss different methods for quantitative assessment of the amount of cargo taken up and how to correlate those numbers with biological effects by applying easy to handle reporter systems. The focus of this article is recent progress in the field of peptide-mediated cellular delivery of siRNA and steric block oligonucleotides in cell tissue culture as a starting point for further developments illustrated by own experimental data. In contrast to many noncovalent CPP-mediated siRNA delivery approaches, efficient splice correction was only achieved with conjugates of peptide and steric block oligonucleotide. As outlined above, our quantitative studies along with microscopic analyses of siRNAs and steric block oligonucleotides using either a peptide or a commercially availably cationic lipid as carrier clearly show that less than 0.1% -5% of molecules taken up are involved in a biological response, i.e. RNAimediated down regulation or splice correction-mediated up regulation of reporter gene activity.
cord-000264-o80duxhs	2009	
cord-000947-psguw47w	2013	
cord-001677-p6ikd8ns	2015	To this end, we utilized sites in the hexon hypervariable region (HVR) 7, 8 and 9 to display a 15-mer peptide containing the main neutralizing epitope of porcine reproductive and respiratory syndrome virus. In this study, we explored different sites in HVRs 7, 8 and 9 of hAd5 hexon for the insertion of a peptide corresponding to the porcine reproductive and respiratory syndrome virus (PRRSV) main neutralizing epitope B [19] of the GP5 protein. In the current study, we find a new site in HVR7 for incorporation of foreign peptide into hAd5 hexon, and determine that the peptide was also exposed on the virion surface making it readily accessible for antibody binding and be potentially useful for vaccination. Herein, we report a novel adenovirus vector (Ad5HVR7epB) with the insertion of the PRRSV main neutralizing epitope B in 3 different HVR regions of the major capsid protein hexon.
cord-001726-d7iwkatn	2015	Particular emphases are placed on: (i) the advantages of the phage as a vaccine carrier, including its high immunogenicity, relative antigenic simplicity and ability to activate a range of immune responses, (ii) the phage''s potential as a prophylactic and therapeutic agent for infectious and chronic diseases, (iii) the regularity of the virion major coat protein lattice, which enables a variety of bioconjugation and surface chemistry applications, particularly in nanomaterials, and (iv) the phage''s large population sizes and fast generation times, which make it an excellent model system for directed protein evolution. While in some cases the results of these studies have been promising, antibody epitope-based peptide vaccines are no longer an area of active research for several reasons: (i) in many cases, peptides incompletely or inadequately mimic epitopes on folded proteins (Irving et al., 2010 ; see below); (ii) antibodies against a single epitope may be of limited utility, especially for highly variable pathogens (Van Regenmortel, 2012); and (iii) for pathogens for which protective immune responses are generated efficiently during natural infection, peptide vaccines offer few advantages over recombinant subunit and live vector vaccines, which have become easier to produce over time.
cord-001835-0s7ok4uw	2015	Altogether, these results indicate that, although PHDs might be more selective for HIF as a substrate as it was initially thought, the enzymatic activity of the prolyl hydroxylases is possibly influenced by a number of other proteins that can directly bind to PHDs. Non-natural aminoacids via the MIO-enzyme toolkit Alina Filip 1 , Judith H Bartha-V ari 1 , Gergely B an oczy 2 , L aszl o Poppe 2 , Csaba Paizs 1 , Florin-Dan Irimie 1 1 Biocatalysis and Biotransformation Research Group, Department of Chemistry, UBB, 2 Department of Organic Chemistry and Technology An attractive enzymatic route to enantiomerically pure to the highly valuable a-or b-aromatic amino acids involves the use of aromatic ammonia lyases (ALs) and aminomutases (AMs). Continuing our studies of the effect of like-charged residues on protein-folding mechanisms, in this work, we investigated, by means of NMR spectroscopy and molecular-dynamics simulations, two short fragments of the human Pin1 WW domain [hPin1(14-24); hPin1(15-23)] and one single point mutation system derived from hPin1(14-24) in which the original charged residues were replaced with non-polar alanine residues.
cord-002141-9mxi4dzi	2016	
cord-002394-n85ptr5p	2017	
cord-003020-q69f57el	2018	
cord-003033-nlaiurau	2018	
cord-003084-y4w3plro	2018	
cord-003948-npijn7co	2019	title: Performance evaluation of antimicrobial peptide ll-37 and hepcidin and β-defensin-2 secreted by mesenchymal stem cells mesenchymal stem cells (MSCs) are key to produce antimicrobial peptides and to inhibit the growth of pathogens. The purpose of this review was to investigate the targets and mechanisms of antimicrobial peptides secreted by MSCs. Antibiotics are used to treat bacterial infections through either inhibiting or killing the target bacteria. Recent studies have found that MSCs play an important role in the treatment of diseases, including infections, by producing antimicrobial peptides [12, 13, 14] . Due to the unique characteristics of antimicrobial peptides, these peptides are one of the main candidates in the treatment of bacterial diseases and are effective on antibiotic resistant strains and even cancer cells. Antibacterial effect of human mesenchymal stem cells is mediated in part from secretion of the antimicrobial peptide LL-37
cord-007735-ejvv2lxv	2006	The expression of certain β-defensins is inducible upon stimulation with bacterial components or pro-inflammatory cytokines and thus these peptides are presumed to be an important component of host defence to infection or inflammation. The difficulties in assessing the role of host defence peptides in vivo are profound, as it is almost impossible to account for synergistic interactions between peptides and other factors, to assess the actual concentrations at the sites of infection and to discriminate the direct antimicrobial activity of peptides from other less direct effects such as enhancement of inflammatory mechanisms (chemotaxis and recruitment of effector cells, enhancement of nonopsonic phagocytosis, etc.). It appears that host defence peptides induce chemotaxis in two ways: first through direct chemotactic activity of PMNs and mononuclear cells mediated through CCR6 and other as yet to be identified receptors and second through inducing chemokine production which would hypothetically increase the numbers of neutrophils and monocytes at sites of infection.
cord-007755-o2r8ktie	2014	
cord-009492-lhwhkada	2007	Novel developments in individual CE and CEC modes are shown and several types of their applications to peptide analysis are presented: conventional qualitative and quantitative analysis, purity control, determination in biomatrices, monitoring of chemical and enzymatical reactions and physical changes, amino acid and sequence analysis, and peptide mapping of proteins. Preconcentration and preseparation (or "sample cleanup") are the necessary operations for sample preparations, when separation power and/or sensitivity of CE and CEC are not sufficient for direct analysis of peptides present at low concentration levels and/or in complex mixtures of different (bio)matrices, such as body fluids, cell lysates, and tissue extracts. After optimization the injection conditions, such as type and concentration of the acid and organic solvent in the sample solution, length of the water plug, sample injection time, and separation voltage, more than 3000-fold improvement in detection signal was obtained, permitting analysis of bioactive peptides and tryptic protein digests in low nanomolar (fmol/mL) levels.
cord-009743-2rntyccn	2008	
cord-011184-ohdukhqt	2019	
cord-012391-53hgrs40	2020	
cord-013364-pq9obtrc	2020	
cord-013952-zp4q3ztr	2020	Biosynthesis of lanthionine-constrained peptides exploiting engineered Gram-positive or Gram-negative bacteria that contain lanthionine-introducing enzymes constitutes a convenient method for discovery of lanthionine-stabilized GPCR agonists. The nisin precursor peptide is dehydrated by the dehydratase NisB [26, 27] , after which a cyclase NisC [28] couples dehydroamino acids to cysteines followed by export by the transporter NisT and removal of the leader peptide by the extracellular leader peptidase NisP [29] . While the attainment of strict rules with respect to the substrate specificities of lanthionine-introducing enzymes has been challenging, some practical guidelines for the design of modifiable peptides have been reached for some lanthipeptide biosynthesis systems [32] . The stereospecificity of NisC-cyclized GPCR agonist, 4,7 lanthionine-angiotensin-(1-7) was investigated using the Ni 2 B method, which opens the ring structure while retaining the D or L conformation [43] . In addition, the feasibility of highthroughput screening for tailor-made lanthionine-introducing enzymes with adapted substrate specificity for rational design and biosynthesis of lanthipeptide GPCR agonists has recently been demonstrated.
cord-018401-josb16pi	2014	
cord-022499-7d58f1k3	2004	For example, if effects were averaged over three shells of lipids, changes in fatty acyl chain lengths by 4 and 10 carbons from that giving optimal interaction would decrease lipid-protein binding constants by factors of 1.6 and 21, respectively. These results suggest that the effects of charge on the interactions between phospholipids and transmembrane ot helices will often be rather small and will be strongly dependent on the detailed structure of the peptide and its orientation in the membrane. However, there is evidence for the presence of a small number of "special" anionic phospholipids binding to some membrane proteins, acting as "cofactors." An example is provided by cytochrome c oxidase, whose crystal structure shows the presence of a lipid molecule bound between the transmembrane a helices (Iwata et al., 1995) . It could therefore be that matching of the thickness of the lipid bilayer and the transmembrane length of the protein is important in retention in ER, as was suggested for the Golgi complex.
cord-022779-himray6q	2005	Here we present a novel strategy to synthesize proteins through a chemical ligation using unprotected peptide segments. Using short portions (7-11 amino acid) rich in positively charged residues from either human lactoferricin or the MARCKS protein as templates, a panel of 70 peptides each possessing a specific chemical structure was synthesized. Subsequent functionalization of such azide groups via Staudinger or "Click" chemistry should provide a convenient method for linking proteins with a diverse array of probes, biomolecules, surfaces and other materials under mild conditions. Moreover, the advantages of peptide and protein chemical synthesis over recombinant-DNA methods are increasingly being used to provide rapid structure-activity information of complex bioactive peptides, small proteins and functional receptor domains. Thus, these new peptides bear all of the requirements which are necessary for formation of cooperatively interacting helical structures and, furthermore, contain domains for cooperative sheet aggregation as well.
cord-022955-vy0qgtll	2005	In order to understand the molecular basis of the enzyme-substrate binding mechanism, we employ the synthetic peptide and mass spectrometry-based approaches to investigate the significance of selected amino acid residues that are flanking both sides of the SARS-CoV 3CL pro cleavage site. To contribute to the assignment of a physiological role to genomic-derived peptidases and to make them more accessible for the drug discovery process, we have undertaken a program consisting of mRNA expression profiling, full-length recombinant expression in insect cells, purification and determination of the catalytic activity for the human proteolytic enzymes. This comprehensive analysis of the local backbone properties of SGTI in the free and in the complex form made possible to identify conformational similarities and differences responsible for its efficient binding to the enzyme, and provides a good basis for further studying the structural aspects of protease inhibitor specificity.
cord-023200-3caevjvh	2018	
cord-023208-w99gc5nx	2006	In order to develop a synthetic protocol by an automated instrumentation, increasing yield, purity of the crude, and reaction time, a microwave-assisted solid phase peptide synthesis was validated comparing the use of the new generation of Triazine-Based Coupling Reagents (TBCRs) with a series of commonly used ones. Ubiquitinium is a well known mechanism in protein degredation of Eukaryotic cells ,in which many obsolte and corrupted three dimentional structure protein ,become marked by covalent attachment of ubuquitin through a multi-step enzymatic pathway.Ubiquitin is a small ,8.5 kDa peptide of 76 amino acid residues that targets such substrtes for proteolysis in proteasome .Recnt studies showed that an extra cellular ubiquitination process also taking place in the epididymes of humans and other animals marks protein on the surface of the defective sperm .it appears that structurally and functionally defective sperm become surface ubiquitinated by epididymal epithelial cells. This head-to-tailcyclized 14-amino-acid peptide contains one disulfide bridge and a lysine residue (Lys5) present in the P1 position, which is responsible for inhibitor specificity.As was reported by us and other groups, SFTI-1 analogues with one cycle only retain trypsin inhibitory activity.
cord-023209-un2ysc2v	2008	Site-specifi c PEGylation of human IgG1-Fab using a rationally designed trypsin variant In the present contribution we report on a novel, highly selective biocatalytic method enabling C-terminal modifi cations of proteins with artifi cial functionalities under native state conditions. Recently, our group report a novel approach to a totally synthetic vaccine which consists of FMDV (Foot and Mouth Disease Virus) VP1 peptides, prepared by covalent conjugation of peptide biomolecules with membrane active carbochain polyelectrolytes In the present study, peptide epitops of VP1 protein both 135-161(P1) amino acid residues (Ser-Lys-Tyr-Ser-Thr-Thr-Gly-Glu-Arg-Thr-Arg-Thr-Arg-Gly-Asp-Leu-Gly-Ala-Leu-Ala-Ala-Arg-Val-Ala-Thr-Gln-Leu-Pro-Ala) and triptophan (Trp) containing on the N terminus 135-161 amino acid residues (Trp-135-161) (P2) were synthesized by using the microwave assisted solid-phase methods. Using as a template a peptide, already identifi ed, with agonist activity against PTPRJ(H-[Cys-His-His-Asn-Leu-Thr-His-Ala-Cys]-OH), here we report a structure-activity study carried out through endocyclic modifi cations (Ala-scan, D-substitutions, single residue deletions, substitutions of the disulfi de bridge) and the preliminary biological results of this set of compounds.
cord-023225-5quigar4	2012	To further explore the structure-function relationship, a viable synthesis strategy for pseudodesmin A analogues was developed, based on side-chain attachment of the first amino acid to the solid support, followed by stepwise Fmoc solid-phase synthesis of the linear peptide precursor and on-resin head-to-tail cyclization. The cases when the amino acid sequence of a fragment coincided with part of the primary structure of a natural oligopeptide were recorded in the Total protein chemical synthesis requires a case by case design and optimization which is governed by factors such as the solubility of the individual peptide segments, their primary sequence and in particular the presence of "difficult" amino acid residues at ligation junctions such as proline or the location of cysteines. In this study we present synthesis of two series of peptide libraries, which were designed by substitution of Leu in the P5, P6 position of our control peptide (Ac-LLLLRVKR-AMBA) with each of nineteen amino acid residues in order to verifying its influence on activity and selectivity of the resulting analogues.
cord-024193-khdvj6t5	2012	
cord-031957-df4luh5v	2020	19 Plant AMPs are the central focus of the present review, comprising information on their structural features (at genomic, gene, and protein levels), resources, and bioinformatic tools available, besides the proposition of an annotation routine. 26 Plant AMPs are also classified into families considering protein sequence similarity, cysteine motifs, and distinctive patterns of disulfide bonds, which determine the folding of the tertiary structure. 27, 31 These AMP categories will be detailed in the next sections, together with other groups here considered (Impatienlike, Macadamia [β-barrelins], Puroindoline (PIN), and Thaumatin-like protein [TLP]) and the recently described αhairpinin AMPs. The description includes comments on their structure, pattern for regular expression (REGEX) analysis (when available), functions, tissue-specificity, and scientific data availability. 179 As to the TLP structure, this protein presents characteristic thaumatin signature (PS00316): 180, 181 Most of the TLPs have molecular mass ranging from 21 to 26 kDa, 163 possessing 16 conserved cysteine residues (Supplementary Figure S8) involved in the formation of 8 disulfide bonds, 182 which help in the stability of the molecule, allowing a correct folding even under extreme conditions of temperature and pH.
cord-048360-n9sih438	2007	
cord-103421-46owvqw8	2020	Improvements include: ingestion of complex sequence assembly data categories (metagenomic and metatranscriptomic assemblies, single cell amplified genomes, and metagenome assembled genomes), prediction of the Least Common Ancestor (LCA) for a peptide shared across multiple organisms, increased performance through updates to the backend architecture, and development of a web portal (https://metatryp.whoi.edu). Improvements include: ingestion of complex sequence assembly data categories (metagenomic and metatranscriptomic assemblies, single cell amplified genomes, and metagenome assembled genomes), prediction of the Least Common Ancestor (LCA) for a peptide shared across multiple organisms, increased performance through updates to the backend architecture, and development of a web portal (https://metatryp.whoi.edu). This feature previously existed in METATRYP v 1 for generating peptide redundancy tables within the "Genome" sequencing data category and was used to show the relatively low occurrence of shared peptides across disparate taxa in the open ocean microbiome [1] .
cord-103837-iuvigqdx	2020	Mass spectrometry is used to identify 526 unique sequences from SARS-CoV-2 spike glycoprotein extracellular domain in a complex with human leukocyte antigen class II molecules on antigen presenting cells from a panel of healthy donors selected to represent a majority of allele usage from this highly polymorphic molecule. The ability to automate and miniaturize the MAPPs assay enables facile identification of 1000''s of naturally processed and displayed HLA-II peptides from human DCs. Using this approach, we were able J o u r n a l P r e -p r o o f to determine the precise regions and sequences of peptides from SARS-CoV-2 spike glycoprotein ECD derived from a panel of healthy subjects presented for immune surveillance by T-cells. We observed a total of 526 unique peptide sequences contained within 73 clusters distributed across each segment of the SARS-CoV-2 spike glycoprotein ECD presented by human DCs (Figure 2 and Supplemental Table S2 ).
cord-252147-bvtchcbt	2011	Modular protein engineering, virus-like particles (VLPs), and other self-assembling entities are envisioned as modulatable novel protein nanoparticles able to include many desirable properties in the correct delivery of drugs and nucleic acids. 120 Modular fusion proteins that combine distinct functions required for cell type-specific uptake and intracellular delivery of DNA or drugs present an attractive approach for the development of self-assembling vectors for targeted gene or drug delivery. 215, 216 Although VLP-based vaccines have been primarily developed for their use against the corresponding virus, in the last decades genetic engineering or chemical modifications have been applied in order to generate chimeric VLPs. Thus, on the one hand, commonly short heterologous peptide epitopes or full proteins that are unable to form VLPs or that are unsafe for vaccination have been presented on surface-exposed loops or fused to N-or C-exposed termini of structural viral capsid proteins on VLPs. 154, 161, 210 Different HPV, 217-219 HBV, 220,221 parvovirus, 222, 223 and chimeric polyoma VLPs have been engineered 170, 175 and tested for different applications including vaccination against viral or bacterial diseases, against virus-induced tumors, and more recently, for immunotherapy of nonviral cancer.
cord-254404-lrsqrc2u	2020	Analysis of transcriptome/genome sequence data revealed loss of NPY/NPF-type signalling, but orthologs of PrRP-type neuropeptides and sNPF/PrRP-type receptors were identified in echinoderms. A more recent finding was the discovery of a family neuropeptide precursor-type proteins in echinoderms that contain a peptide that shares sequence similarity with NPY/NPF-type peptides (Zandawala et al., 2017) . rubens neuropeptide and orthologs from other echinoderms with related peptides in other taxa revealed that they share sequence similarity with both PrRP-type neuropeptides ( Figure 1A ) and with NPY/NPF-type neuropeptides ( Figure 1B) . In echinoderm PrRP-like peptide genes, the exon encoding the neuropeptide is likewise interrupted by an intron but it is located in a different position to the intron that interrupts the coding sequence for NPY/NPF-type peptides. Subsequently, analysis of transcriptomic/genomic sequence data has enabled identification of NPY/NPF-type neuropeptides and their cognate receptors in a variety of invertebrate taxa, revealing a high level of conservation of this signalling system in bilaterian phyla (Zatylny-Gaudin and Favrel, 2014; Fadda et al., 2019) .
cord-257494-242k58ll	2017	1 Human host defense peptides are an intrinsic part of the innate immune system and exhibit a broad activity spectrum against bacteria, fungi, viruses, and parasites While AMPs can be antibacterial (ABPs), antifungal, antiprotist, antiviral, anticancer, antiparasitic, insecticidal, spermicidal, chemotactic, antioxidant, protease inhibitors, or even exhibit wound healing properties (Supporting Information Table S1), their scope of action overlaps considerably and some peptides show activity at several levels (Fig. 2 ). 75 Moreover, when stabilizing disulfide bridges between conserved cysteine residues in human AMPs with β-hairpin or β-sheet conformations are disrupted, the resulting linear peptides still maintain their antimicrobial properties despite losing membranolytic activity. 212, 213 However, it should be noted that the antimicrobial effects of encephalins and their derived peptides result mostly from animal studies and have not been adequately studied in human secretions, despite the high conservation of their sequences across species, which most likely contribute for the similar activity spectrum.
cord-260392-hj9s5cnu	2008	
cord-262253-3ovqhypt	2020	The aggregation and accumulation of amyloid-β plaques and tau proteins in the brain have been central characteristics in the pathophysiology of Alzheimer''s disease (AD), making them the focus of most of the research exploring potential therapeutics for this neurodegenerative disease. The present review will highlight the current understanding of amyloid-β, and the role of bacteria and viruses in AD, and will also explore the therapeutic potential of antimicrobial and antiviral drugs in Alzheimer''s disease. Alzheimer''s Disease Aβ amyloid-β AMP antimicrobial peptide APP amyloid precursor proteins BACE1 B-site ABPP cleaving enzyme BBB blood brain barrier CNS central nervous system HSV-1 herpes simplex virus-1 MBP-1 major basic protein-1 NFTS neurofibrillary tangles Protective Effect of Amyloid-beta Peptides Against Herpes Simplex Virus-1 Infection in a Neuronal Cell Culture Model The Alzheimer''s disease-associated amyloid beta-protein is an antimicrobial peptide Antivirals reduce the formation of key Alzheimer''s disease molecules in cell cultures acutely infected with herpes simplex virus type 1
cord-262748-v4xue7ha	2015	
cord-269462-7yozebv2	2010	METHODS: Fusion peptides of several enveloped viruses belonging to different virus families were prepared by standard 9-fluorenylmethoxycarbonyl polyamine solid-phase synthesis and used to stimulate U937 cells in vitro to analyze the phosphorylation patterns of the signaling pathways (PKC, Src, Akt, and MAPK pathways). Specific ligand-receptor interactions result in activation of signaling pathways; thus, we selected fusion peptides belonging to each of the known viral classes of fusion glycoproteins in order to verify whether during the interaction with the cell surface, they were sufficient to induce phosphorylation of PKC, Src, Akt, and MAPK pathways, activation of nuclear factor (AP-1 and NF-B), and cytokine release (IL-10 and IFN-␤ ). To selectively analyze the regulation of virus-induced AP-1 and NF-B activation, an ELISA-based Trans-Am technology from nuclear lysates of U937 cells stimulated by viral fusion peptides was performed.
cord-269756-tid8a464	2016	Although membrane fusion promoted by class I viral glycoproteins, such as SARS-CoV Spike, human immunodeficiency virus (HIV) gp160 or influenza virus hemagglutinin (HA), has been broadly studied in recent years [16] [17] [18] [19] , many aspects of the molecular mechanism behind the virus-host cell membrane fusion remain unknown, including conformational changes of the lipid bilayers during peptide-membrane interactions. In the present study, we investigated the effects of two putative fusion peptides from SARS-CoV S glycoprotein, corresponding to residues 770-788 (SARS FP ) and 873-888 (SARS IFP ) 13, 15, 22, 23 , on the structural dynamics, physicochemical properties, and thermotropic phase behavior of lipid model membranes by differential scanning calorimetry (DSC), continuous wave (CW) and pulsed electron spin resonance (ESR) along with nonlinear least-squares (NLLS) spectral fitting 24 .
cord-273107-xc61osdx	2014	
cord-274101-vm9nh8lc	2012	The separation occurs because of highly specific biochemical interactions between the peptide and the ligand Used when a high degree of specificity is required, for example, isolation of a target protein present in low concentration in a biological fluid or a cell extract Capillary electrophoresis Based on the migration of the peptide according to its charge in solution, depending on the application of an electric field. Peptides have shown various bioproperties, among them antimicrobial activity, leading to the application of these compounds in the food preservation area by either direct addition or incorporation into packaging materials (Table 8) . Active packaging materials incorporated with antimicrobial peptides have shown effectiveness in inhibiting pathogenic microorganisms, an improvement in food safety. Several studies have indicated significant changes in mechanical properties and surface morphology of the films incorporated with antimicrobial peptides.
cord-277716-6gsmkmk5	2015	RESULTS: Here, we were studying in vitro and in silico the effect of the chain length and of point mutations near the linker region between the pentamer and the trimer on the self-assembly of the SAPNs. 60 identical peptide chains co-assemble to form a spherical nanoparticle displaying icosahedral symmetry. All these different mutants along with the initial parent peptide (Fig. 3) were studied by molecular dynamics (MD) simulations using the program CHARMM 36b1 in an attempt to further optimize the linker region and find the best peptide building block for the SAPNs. From the linker constitution study it was found that a malaria nanoparticle vaccine construct self-assembled into almost spherical nanoparticles [21] . Based on our construct design and the biophysical results of the 2.5HR we ran a series of molecular dynamics simulations on the eleven short versions of 2.5HR including only five helical turns (i.e. 2.5 heptad repeats) around the linker region of the nanoparticle peptide (Figs.
cord-280383-hi7z3nob	2010	In this study, we present SAROTUP, a free web tool for scanning, reporting and excluding possible target-unrelated peptides from real mimotopes. There are now quite a few programs for mimotope based epitope mapping, none of them, however, has a procedure to scan, report and exclude target-unrelated peptides [15] [16] [17] [18] [19] [20] [21] [22] [23] . It is capable of finding, reporting, and precluding possible target-unrelated peptides, which is very helpful for the development of mimotope-based diagnostics, therapeutics, and vaccines. Scott reviewed a collection of target-unrelated peptides recovered in the screening of phage-displayed random peptide libraries with antibodies [12] . Although SAROTUP looks a little bit Table 2 , the first test data set has 11 panels of peptides acquired from phage display libraries screened with 8 targets. Furthermore, SAROTUP will not only benefit the mimotope-based epitope mapping, but also the development of new diagnostics, therapeutics, and vaccines.
cord-284523-lknyehsa	2017	
cord-284690-ogu1gmcb	2016	The use of viral vectors based on the tobacco mosaic virus (TMV) and potato virus X (PVX) for cloning and massively expressing AMP genes in Nicotiana benthamiana appears to be an interesting new approach to considerably enhance recombinant peptide production before structural and functional characterization. However, frequent gene silencing at the transcriptional level and instability of genes cloned in vectors for stable or transient expression remain major challenges limiting the efficient production of AMPs. Another persistent issue is the poor quality of the peptides endogenously synthesized in bacteria, yeast, and plants, particularly resulting from undesirable post-translational modifications [2, 33] . Some drawbacks presented by plant expression systems are solved by the CRISPR system, a revolutionary genome-editing technology that presents myriad possibilities for genetic manipulation at the genomic level and provides unprecedented tools (CRISPRi and CRISPRa) to precisely control gene expression and the structural modification of AMPs. Despite its current minor limitations (e.g. off-target effects), CRISPR could have a key role in the future development of clinical drugs as biotechnological antiinfective agents, including the rational biosynthesis of next-generation antimicrobials.
cord-285443-9y2kkmby	2014	The combination of bioinformatic lead identification and potency/pharmacokinetics improvement provided by cholesterol conjugation may form the basis for a rapid response strategy, where development of an emergency cholesterol‐conjugated therapeutic would immediately follow the availability of the genetic information of a new enveloped virus. For example, although the entry of herpes viruses (featuring a class III fusion protein) is a complex process, not yet fully clarified, in which multiple glycoproteins are involved, several laboratories have reported that peptides derived from the HR regions of gB and gH of herpes simplex virus type 1, bovine herpes virus type 1, and human cytomegalovirus are able to inhibit infection [103] . Given the ubiquitous importance of cholesterol-rich lipid rafts in viral fusion, it is expected that cholesterol conjugation may enhance the antiviral potency also for peptides derived from class II and III fusion proteins. Antiviral activity of membrane fusion inhibitors that target gp40 of the feline immunodeficiency virus envelope protein
cord-287123-ldkuwcc7	2017	The formyl peptide receptors (FPRs) are G protein-coupled receptors that transduce chemotactic signals in phagocytes and mediate host-defense as well as inflammatory responses including cell adhesion, directed migration, granule release and superoxide production. N-formylated peptides constitute the most commonly studied class of FPR agonists that trigger a variety of biological activities in myeloid cells, such as chemokinesis, chemotaxis, calcium flux, cytokine production and superoxide anion generation. Through binding with the high affinity receptor FPR1, fMLF and other N-formylated peptides serve as potent chemoattractants, which also include activated complements (C5a, C3a) and chemokines, in recruiting and guiding leukocytes to the site of bacterial infection and to damaged tissues. As the first identified endogenous peptide agonist for FPR [56] , documented studies have shown that it exerts pro-inflammatory activities through FPR2 in phagocytes, epithelial cells and T lymphocytes, including stimulating production of inflammatory mediators and enhancing the expression of cytokine receptors [109] [110] [111] [112] [113] .
cord-289161-d7shmb2o	2014	This review aims to provide an examination of AMPs from scorpion venom (Table 1; Fig. 1 ), with discussions on structure, biological activity and proposed mechanisms of action, together with a final discussion of recent and future strategies for mining new bioactive molecules. This substitution creates a more flexible region while retaining the essential amphipathic nature of Pin 2 which is more in tune with the dual helical structure of Corzo, Nakajima and colleagues have subsequently demonstrated that the haemolytic activity of Pin1, Pin2 and other cationic amphipathic peptides (e.g. IsCt1, see Section 3.3) depends on the animal species studied (guinea pig > pig > sheep) and this is turn is related to the phosphatidylcholine:sphingomyelin ratio in the different erythrocyte membranes (Belokoneva et al., 2003) . CD spectral analysis of synthetic meucin-24 (2.8 kDa, 24 amino acids) showed a disordered conformation in water; however a-helical formation increased in 50% TFE and NMR spectra revealed an a-helical structure between residues 4e20 and random coil regions at the N-and C-terminals (Gao et al., 2010) .
cord-291534-c6cjxq07	2013	
cord-293072-giakcaki	2017	
cord-295207-0p6x4lwx	2011	The aim of this study was to develop therapeutic peptides targeting glycoprotein B (gB), a major glycoprotein of HCMV that is highly conserved across the Herpesviridae family, that specifically inhibit fusion of the viral envelope with the host cell membrane preventing HCMV entry and infection. Previous studies have suggested that synthetic peptides corresponding to or overlapping with sequences in viral fusion proteins that have positive WWIHS scores can sometimes serve as viral entry inhibitors [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] [45] [46] [47] [48] [49] [50] . For example, Enfurvitide (Fuzeon) is a 36-amino acid peptide that overlaps with a WWIHS score-positive sequence in the transmembrane protein (TM) of HIV-1, and prevents viral fusion and entry of the virus. These results suggest that the HCMV inhibitory peptides identified here may serve as Figure 2 Determination of regions within gB that display a high propensity to interact with the lipid surface of cell membranes by using Wimley-White Interfacial Hydrophobicity Scale (WWIHS).
cord-298019-gf2asni1	2014	While they have been initially discovered in viral fusion proteins and have been involved in the mechanism of viral entry, it is now clear that their features and their mode of interaction with membrane bilayers can be exploited to design viral inhibitors as well as to favor delivery of cargos across the cell membrane and across the blood–brain barrier. Peptides with a propensity for membrane binding can also interfere with enveloped virus entry by direct physical interaction with the hydrophobic surfaces present on cell membranes and/or fusion proteins. Since not all membranotropic peptides are able to cross the membrane bilayer, it is essential to identify structural characteristics of hydrophobic peptides know to enter the cell membrane to highlight any feature that is involved in the penetration which may help in the design of novel delivery tools. Dendrimer functionalization with a membrane-interacting domain of herpes simplex virus type 1: towards intracellular delivery
cord-300189-gsp1dozg	2017	To date, few peptide molecules outside the well-known inhibitory regions of Class 1 viral fusion proteins, the heptad repeats, should be as fusion; therefore, a brute force approach to the identification of peptide entry inhibitors may help in the dissection of HSV-1 glycoproteins domains. Previous works using a physico-chemical algorithm, the Wimley-White Interfacial Hydrophobicity Scale (WWIHS), in combination with other structural data allowed us to predict regions in gH potentially involved in membrane interactions during the entry and fusion process, and some of them were found to possess HSV antiviral activity in dose-dependent inhibition assays [66] . [76] used a phage display methodology to identify a peptide (named P1) to inhibit West Nile virus (WNV) infectivity, possibly by binding to the envelope glycoprotein (E protein) necessary for membrane fusion. Substitution of herpes simplex virus 1 entry glycoproteins with those of saimiriine herpesvirus 1 reveals a gD-gH/gL functional interaction and a region within the gD profusion domain that is critical for fusion
cord-305755-6jup93v4	2020	
cord-307909-7vbxyns0	2020	
cord-314604-w61sqy17	2020	
cord-315115-f61xcnuw	2020	title: Bioinformatic Analysis of 1000 Amphibian Antimicrobial Peptides Uncovers Multiple Length-Dependent Correlations for Peptide Design and Prediction For this study, we found 1015 frog antimicrobial peptides in the APD3, ranging from 5 to 63 amino acids (an average length of 24) [78] . Antibiotics 2020, 9, x FOR PEER REVIEW 4 of 26 For this study, we found 1015 frog antimicrobial peptides in the APD3, ranging from 5 to 63 amino acids (an average length of 24) [78] . These numbers can be regarded as minimal since many predicted/isolated AMPs without Antibiotics 2020, 9, 491 5 of 26 antimicrobial activity data or those tested to be inactive (MIC > 100 µM) are not included in our analysis. This study focuses on amphibian peptides with demonstrated antimicrobial activity collected in the APD database. Isolation, amino acid sequence, and synthesis of dermaseptin, a novel antimicrobial peptide of amphibian skin
cord-316474-407bthqj	2011	Since the pioneering work described above, phage display technology has further been developed and improved by scientists from various fields, and its applications has extended from epitope mapping to antibody engineering and organ targeting [2] [3] [4] [5] . Mimotopes can now be obtained in a relatively cheap, efficient and convenient way, i.e. screening phage-displayed random peptide libraries with a given target. In this review, we will summarize the special databases, algorithms, programs, web servers and their applications in the phage display area, focusing on the tools for mimotope-based epitope mapping. With these tools, phage display technology has shown its power in exploring the interactions between proteins, peptides and small molecule ligands. Powered by special computational tools developed for phage display technology, not only linear epitope but also conformational epitope formed by discontinuous residues brought into spatial proximity by protein folding can be mapped reasonably.
cord-316792-89f8g0m8	2020	Over the course of evolution, toxins with exceptional specificity and high potency for their intended molecular targets have prevailed, making venoms an invaluable and almost inexhaustible source of bioactive molecules, some of which have found use as pharmacological tools, human therapeutics, and bioinsecticides. Current biomedically-focused research on venoms is directed towards their use in delineating the physiological role of toxin molecular targets such as ion channels and receptors, studying or treating human diseases, targeting vectors of human diseases, and treating microbial and parasitic infections. Since many venoms and toxins exert these biological effects through actions on cell membranes, receptors and ion channels, high-throughput techniques assessing changes in cellular signalling have proven particularly insightful. Spider-venom peptides have been crucial for uncovering the key role of ASICs in stroke-induced brain damage, and validating these channels as a target for neuroprotective drugs [134] [135] [136] [137] .
cord-320497-e5pb83mj	2010	
cord-320693-de1lmzl1	2019	
cord-321417-6code4oh	2003	The parent peptides and mBMAP-28 analog protected mice from lethal i.p. infections in an acute peritonitis model at peptide doses significantly lower than those toxic to the animals, suggesting a satisfactory therapeutic index. Specifically, we analysed the in vitro activity of BMAP-27 and -28 and of their analogs against a wide panel of Gramnegative and -positive clinical isolates, also including many antibiotic-resistant strains, and against the human herpes simplex virus type 1 (HSV-1). The in vitro antibacterial activity of purified BMAP peptides and of their analogs was determined as the minimum inhibitory concentration (MIC) by a microdilution susceptibility test in 96-well microtiter plates, according to the guidelines of the National Committee for Clinical Laboratory Standards (NCCLS). The potential of BMAPs to protect mice from a bacterial challenge was tested in a model of acute peritonitis induced by i.p. injection of a lethal dose of P.
cord-331633-ix5un6c9	2020	
cord-332003-67e9fchy	2015	Although challenged later on as detailed in Section 7, this mechanism and the possibility to use such so called cell-penetrating peptides (CPPs) as non-viral delivery vectors for biomolecules, fostered a very large interest. Since the chemical conjugation and purification of negatively charged ONs with the most popular cationic CPPs has turned out to be difficult, most applications have concerned chargeneutral ON analogues such as Peptide Nucleic Acids (PNAs) and PMO (see Section 3). Unexpectedly, in a well-characterized HeLa 705 cell assay with a positive read-out ( Fig. 1) , splicing redirection using PNA or PMO oligomers conjugated to various standard CPPs (Tat, Penetratin or oligo-arginines) was not achieved in our research groups [57] . This led to the development of several arginine-rich peptides as PMO conjugates for use in muscle cells and in vivo mouse models of DMD as outlined in Section 4.
cord-333262-xvfl7ycj	2020	The Wuhan and related isolates revealed a coronavirus that resides in the subgenus Sarbecovirus of the genus Betacoronavirus [2] , and although genetically distinct from its predecessor SARS-CoV it appeared to have similar external binding proteins, meaning here the spike glycoprotein discussed extensively in the present paper. In brief summary, the justifications for the ensemble pharmacophore in the coronavirus case, i.e. the contributions to "fuzziness", include parsimony, that proteins and parts of proteins sometimes have more than one function [12] encouraged by limited numbers of accessible sites (due to e.g. glycosylation) and exemplified by parallel alternative mechanisms of cell entry, multiple methods of drug action, escape from scientific defense measures by virus mutation, polymorphism of human proteins involved, different expression levels of human proteins involved, and the potential problem of the "specter of vaccine development" (concerns about missing the appropriate region of the virus that allows common cold viruses to escape the appropriate immune response).
cord-337812-arivkkj0	2006	
cord-337897-hkvll3xh	2009	
cord-339879-92esdjy9	2012	The BNtAb IgG1 b12 was the first neutralizing MAb selected from a phage-displayed Fab (antibody fragment composed of one constant and one variable domain of the heavy (CH1 and VH) and the light (CL and VL) chains linked together) library derived from an HIV-1-infected donor (See section 3.1.1.1.1.) [41] . At the end of the second round, selected phages displaying longer inserts of 40 to 50 AA corresponding to the N-and C-terminal regions of Gag were identified, revealing the presence of two distinct antigenic regions in Gag. This study demonstrated that gene-fragment phage display could be used to identify epitopes targeted by polyclonal Abs. Although they occur at a very low frequency in humans, antibodies targeting host proteins involved in HIV-1 infection have been reported in immunized animals. Anti-human immunodeficiency virus type 1 human monoclonal antibodies that bind discontinuous epitopes in the viral glycoproteins can identify mimotopes from recombinant phage peptide display libraries
cord-340970-389t032s	2004	
cord-340971-e42g37la	2007	
cord-343791-0vykwml5	2017	These include spherical assemblies such as virus-like particles, designed protein nanoparticles, and peptide amphiphiles (Figure 1) ; and elongated structures such as β-sheet nanofibers, fiber-forming peptide amphiphiles, and filamentous phage (Figure 2) . [17, 18] Owing to their lack of a viral genome, VLP-based vaccines circumvent some risks associated Supramolecular materials composed of proteins and peptides have been receiving considerable attention toward a range of diseases and conditions from vaccines to drug delivery. [19] As alternatives to these previous platforms, VLPs were developed to display an array of epitopes that mimic the surface of native viruses more effectively than subunit or peptide vaccines, thus improving their immunogenic properties. Whereas synthetic peptides are usually not sufficiently immunogenic and require adjuvants, the Burkhard group has developed a self-assembling protein nanoparticle platform that displays both B and T cell epitopes to produce a vaccine with self-adjuvanting qualities.
cord-346816-xys0g8b8	2004	
cord-347661-q9lgliph	2007	The use as antigens of either synthetic peptides (coupled to a carrier protein) or proteins expressed in Escherichia coli is described, and detailed protocols for immunization and preparation of test bleeds are provided. Furthermore, in the context of specific research questions, polyclonal antisera may sometimes even be preferred over monoclonal antibodies since they contain a mixture of immunoglobulin molecules, derived from different B-cell lines in the immunized animal, often recognizing multiple epitopes of the target protein. The antiserum used here was raised against a domain in the C-terminal region of pp1a of the arterivirus EAV (8) and recognizes a large set of processing intermediates and end products, which are indicated by arrowheads: (A) Western blot analysis: EAV-and mock-infected cell lysates were prepared at 8 h postinfection, run on an SDS-polyacrylamide gel, blotted to PVDF membrane, and incubated with the postimmune serum at a 1:1000 dilution.
cord-348432-6jgao58w	2017	
cord-351321-6d2mn5ok	2020	
cord-353815-w35spqqt	2020	This review introduces the progress of research on AMPs comprehensively and systematically, including their classification, mechanism of action, design methods, environmental factors affecting their activity, application status, prospects in various fields and problems to be solved. Tryptophan (Trp), as a non-polar amino acid, has a remarkable effect on the interface region of the lipid bilayer, whereas Arg, as a basic amino acid, confers peptide charge and hydrogen bond interactions, which are essential properties to combine with the bacterial membrane''s abundant anionic component. And it seems that Trp residues play the role of natural aromatic activators of Arg-rich AMPs by ion-pair-π interactions (Walrant et al., 2020) , thereby promoting enhanced peptide-membrane interactions (Chan et al., 2006) . Furthermore, L4H4, which is designed based on the linear cationic amphiphilic peptide magainin, also shows good antibacterial activity and cell penetration properties by inserting four histidine sequences in leucine and alanine (Lointier et al., 2020) .