Development of Highly Selective 1,2,3-Triazole-containing Peptidic Polo-like Kinase 1 Polo-box Domain-binding Inhibitors.

Development of Highly Selective 1,2,3-Triazole-containing Peptidic Polo-like Kinase 1 Polo-box Domain-binding Inhibitors.

Cover Story: Two highly selective triazole-containing peptidic polo-like kinase 1 (Plk1) polo-box domain (PBD)-binding inhibitors (3d in green and 4b in orange) are depicted, binding within the hydrophobic “cryptic” binding pocket on the surface of the Plk1 PBD (light blue). The placement was guided by our previously reported X-ray crystal structure of PBD-bound parent peptide (2a) (PDB accession code: 3RQ7), whose binding pocket is highlighted in yellow. These ligands retain the high PBD-binding affinity of the parent peptide, while showing desirable enhanced selectivity for the PBD of Plk1 relative to the PBDs of Plk2 and Plk3.

Citation: 

See: Development of Highly Selective 1,2,3-Triazole-containing Peptidic Polo-like Kinase 1 Polo-box Domain-binding Inhibitors by Zhao, X.Z.; Tsuji, K.; Hymel, D.; Burke, T.R., Jr. in Molecules 2019, 24, 1488.

Published Date: 
April, 2019