Folding Then Binding vs Folding Through Binding in Macrocyclic Peptide Inhibitors of Human Pancreatic α-Amylase.

ABSTRACT: De novo macrocyclic peptides, derived using selection technologies such as phage and mRNA display, present unique and unexpected solutions to challenging biological problems. This is due in part to their unusual folds, which are able to present side chains in ways not available to canonical structures such as α-helices and β-sheets. Despite much recent interest in these molecules, their folding and binding behavior remains poorly characterized. In this work, we present cocrystallization, docking, and solution NMR structures of three de novo macrocyclic peptides that all bind as competitive inhibitors with single-digit nanomolar K_i to the active site of human pancreatic α-amylase. We show that a short stably folded motif in one of these is nucleated by

SUBMITTER: Goldbach L 

PROVIDER: S-EPMC6700688 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature