INHIBITION OF CHYMOTRYPSIN BY ALKYL PHOSPHONATES - QUANTITATIVE STRUCTURE-ACTIVITY ANALYSIS

A quantitative structure-activity relationship has been formulated for 53 alkyl phosphonates [R2OPO(CH3)SR3] inhibiting chymotrypsin: log ki = 1.47MROR + 0.34MRSR + 1.25σ3* - 1.06I - 3.43 log (β·10MR + 1) - 5.26; log β = -3.85. In this so-called bilinear model, ki is the bimolecular rate constant (m-1 s-1), β is a disposable parameter evaluated by a computerized iterative procedure, MR is the molar refractivity of a substituent, σ3* is Taft's polar parameter, and I is an indicator variable for substituents containing a sulfonium group. The correlation coefficient for this equation is 0.985. This quantitative structure-activity relationship is compared with those previously formulated for the action of chymotrypsin on acylamino acid ester substrates. © 1979.