A medium-firm drug-candidate library of cryptand-like structures on T7 phage: design and selection of a strong binder for Hsp90.
Org Biomol Chem
; 19(1): 146-150, 2021 01 06.
Article
in En
| MEDLINE
| ID: mdl-33095213
ABSTRACT
We designed and synthesized a medium-firm drug-candidate library of cryptand-like structures possessing a randomized peptide linker on the bacteriophage T7. From the macrocyclic library with a 109 diversity, we obtained a binder toward a cancer-related protein (Hsp90) with an antibody-like strong affinity (KD = 62 nM) and the binding was driven by the enthalpy. The selected supramolecular ligand inhibited Hsp90 activity by site-specific binding outside of the well-known ATP-binding pocket on the N-terminal domain (NTD).
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Schiff Bases
/
Drug Design
/
Bacteriophage T7
/
HSP90 Heat-Shock Proteins
/
Ethers, Cyclic
/
Small Molecule Libraries
Type of study:
Clinical_trials
Language:
En
Journal:
Org Biomol Chem
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2021
Document type:
Article
Affiliation country:
Japón