biostudies-literatureFujiwara DJSPS KAKENHI3406-3409https://www.ebi.ac.uk/biostudies/studies/S-EPMC9297947biostudies-literatureUnknown22(24)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 bivalentlChembiochem : a European journal of chemical biologyChemical Modification of Phage-Displayed Helix-Loop-Helix Peptides to Construct Kinase-Focused Libraries.PMC929794726870503Ueda MMihara KTakayama RFujii INakamura YFujiwara DTsumuraya TfalseChemical Modification of Phage-Displayed Helix-Loop-Helix Peptides to Construct Kinase-Focused Libraries.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 bivalentl2021-01-01T00:00:00Z2021 Dec2025-04-04T10:47:34.414Z2025-04-04T10:47:34.414ZS-EPMC92979473460513710.1002/cbic.202100450