Separation of electronic and hydrophobic effects for the papain hydrolysis of substituted N-benzoylglycine esters.
The role of hydrophobic and electronic effects on the kinetic constants kcat and Km for the papain hydrolysis of a series of 22 substituted N-benzoylglycine pyridyl esters was investigated. The series studied comprises a wide variety of substituents on the N-benzoyl ring, with about a 300,000-fold range in their hydrophobicities, and 2.1-fold range in their electronic Hammet constants (sigma). It was found that the variation in the log kcat and log 1/Km constants could be explained by the following quantitative-structure activity relationships (QSAR): log 1/Km = 0.40 pi 4 + 4.40 and log 1/kcat = 0.45 sigma + 0.18. The substituent constant, pi 4, is the hydrophobic parameter for the 4-N-benzoyl substituents. QSAR analysis of two smaller sets of glycine phenyl and methyl esters produced similar results. A clear separation of the substituent effects indicates that in the case of these particular esters, acylation appears to be the rate limiting catalytic step.
Compadre
C M
CM
Department of Biopharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock.
Hansch
C
C
Klein
T E
TE
Petridou-Fischer
J
J
Selassie
C D
CD
Smith
R N
RN
Steinmetz
W
W
Yang
C Z
CZ
Yang
G Z
GZ
D002384:Catalysis; D004563:Electrochemistry; D006626:Hippurates / Q000737:chemistry*; D006868:Hydrolysis; D007700:Kinetics; D010206:Papain / Q000737:chemistry*; D013329:Structure-Activity Relationship
D006626:Hippurates; D010206:Papain