Enhanced inhibitory activity of compounds containing purine scaffolds compared to protein kinase CK2α considering crystalline water.

ABSTRACT: We recently reported novel purine-based CK2α inhibitors using the solvent ordering-based method as virtual screening. Among these, the X-ray crystal structure of a complex with CK2α was determined. The results showed that the crystalline water molecules observed in many previously reported complex structures of CK2α and its inhibitors had been eliminated. We then proposed a structure-based drug design. Since the removal of water molecules would be detrimental to inhibitor binding, new groups of compounds were designed by changing the position of the carboxy group located at the point where a water molecule would be present so as not to eliminate it. Compounds with (E)-2-carboxyethenyl and 3-carboxyphenyl substituted at the 2-position on the purine scaffold showed much higher inhibit

SUBMITTER: Nishiwaki K 

PROVIDER: S-EPMC11042117 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature