Chemical Modification of Phage-Displayed Helix-Loop-Helix Peptides to Construct Kinase-Focused Libraries.

ABSTRACT: Conformationally constrained peptides hold promise as molecular tools in chemical biology and as a new modality in drug discovery. The construction and screening of a target-focused library could be a promising approach for the generation of de novo ligands or inhibitors against target proteins. Here, we have prepared a protein kinase-focused library by chemically modifying helix-loop-helix (HLH) peptides displayed on phage and subsequently tethered to adenosine. The library was screened against aurora kinase A (AurA). The selected HLH peptide Bip-3 retained the α-helical structure and bound to AurA with a K_D value of 13.7 μM. Bip-3 and the adenosine-tethered peptide Bip-3-Adc provided IC₅₀ values of 103 μM and 7.7 μM, respectively, suggesting that Bip-3-Adc bivalentl

SUBMITTER: Fujiwara D 

PROVIDER: S-EPMC9297947 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature