Rational drug-design approach supported with thermodynamic studies - a peptide leader for the efficient bi-substrate inhibitor of protein kinase CK2.

ABSTRACT: Numerous inhibitors of protein kinases act on the basis of competition, targeting the ATP binding site. In this work, we present a procedure of rational design of a bi-substrate inhibitor, complemented with biophysical assays. The inhibitors of this type are commonly engineered by combining ligands carrying an ATP-like part with a peptide or peptide-mimicking fragment that determines specificity. Approach presented in this paper led to generation of a specific system for independent screening for efficient ligands and peptides, by means of thermodynamic measurements, that assessed the ability of the identified ligand and peptide to combine into a bi-substrate inhibitor. The catalytic subunit of human protein kinase CK2 was used as the model target. Peptide sequence was optimized using pept

SUBMITTER: Winiewska-Szajewska M 

PROVIDER: S-EPMC6662822 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature