Design and Application of a DNA-Encoded Macrocyclic Peptide Library
Zhengrong Zhu(GlaxoSmithKline (United States)), Alex Shaginian(GlaxoSmithKline (United States)), LaShadric C. Grady(GlaxoSmithKline (United States)), Thomas O’Keeffe(GlaxoSmithKline (United States)), Xiangguo Shi(GlaxoSmithKline (United States)), Christopher P. Davie(GlaxoSmithKline (United States)), Graham L. Simpson(GlaxoSmithKline (United Kingdom)), Jeffrey A. Messer(GlaxoSmithKline (United States)), Ghotas Evindar(GlaxoSmithKline (United States)), Robert N. Bream(GlaxoSmithKline (United Kingdom)), Praew Thansandote(GlaxoSmithKline (United Kingdom)), Naomi R. Prentice(GlaxoSmithKline (United Kingdom)), Andrew M. Mason(GlaxoSmithKline (United Kingdom)), Sandeep Pal(GlaxoSmithKline (United Kingdom))
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Abstract
A DNA-encoded macrocyclic peptide library was designed and synthesized with 2.4 × 1012 members composed of 4–20 natural and non-natural amino acids. Affinity-based selection was performed against two therapeutic targets, VHL and RSV N protein. On the basis of selection data, some peptides were selected for resynthesis without a DNA tag, and their activity was confirmed.
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