id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-103648-g50g17ti	Wang, Hao-Yuan	Total synthesis and biological characterization of SR-A3, a ternatin-related eEF1A inhibitor with enhanced cellular residence time	2020-10-08		.txt	text/plain	2175	124	48	Ternatin and related cyclic peptides inhibit the elongation phase of protein synthesis by targeting the eukaryotic elongation factor-1α (eEF1A), a potential therapeutic vulnerability in cancer and viral infections. Based on our hypothesis that A3 is structurally related to the anti-adipogenic cyclic heptapeptide, ternatin, 9 we previously designed and synthesized "ternatin-4", which incorporates the dehydromethyl leucine (dhML) and pipecolic acid residues found in A3, yet lacks the b-hydroxy group attached to N-Me-Leu ( Figure 1 ). Similar to ternatin-4, SR-A3 potently inhibited cell proliferation and protein synthesis by targeting eEF1A. Whereas protein synthesis rates partially recovered in cells treated with ternatin-4 or SS-A3 (~30% of DMSO control levels, 24 h post-washout), transient exposure of cells to SR-A3 resulted in sustained inhibition (Figure 6a ). Rather, SR-A3 exhibits a dramatic increase in cellular residence time, as revealed by washout experiments followed by assessment of protein synthesis and cell proliferation rates.	./cache/cord-103648-g50g17ti.txt	./txt/cord-103648-g50g17ti.txt