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Insights from ab initio quantum chemical calculations into the preferred tautomeric forms and binding affinities to CDK2 of substituted pyrazolopyridines
Author(s) -
Duca José S.,
Madison Vincent S.
Publication year - 2005
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.20218
Subject(s) - affinities , chemistry , tautomer , quantum chemical , binding affinities , ab initio , computational chemistry , quantum , ab initio quantum chemistry methods , stereochemistry , organic chemistry , molecule , quantum mechanics , biochemistry , physics , receptor
Ab initio calculations were employed to compute pKa values and tautomer properties of a series of substituted pyrazolopyridines. The results show that the neutral 1H tautomer predominates, but upon protonation this proton migrates to give the preferred charged [2H,7H] tautomer. The basicity of the pyrazolopyridines is correlated with the electron donating capability of the 4‐substituent. Ab initio free energy calculations were also used to identify determinants of binding affinity for some recently published pyrazolopyridine inhibitors of CDK2. Hydrogen‐bonding affinity may be one important component of binding strength. © 2005 Wiley Periodicals Inc. Biopolymers (Pept Sci), 2005