QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS OF CHYMOTRYPSIN-LIGAND INTERACTIONS - ANALYSIS OF INTERACTIONS IN RHO-3 SPACE

Fourteen derivatives of l-alanine of the type CH3CH(NHCO-3-C5H4N)COOR3 have been synthesized and their hydrolysis by chymotrypsin was studied with the object of characterizing enzymic space (ρ{variant}3) to which R3 binds. The binding of R3 (log 1 Km) was shown via correlation analysis to correlate with molar refractivity (MR) of R3 rather than hydrophobicity (π). The results confirmed our earlier predictions. A correlation equation for the hydrolysis of 77 acyl-amino acid esters of the general formula R2CH(NHCOR1)COOR3 relating log (kcat km) to molar refractivity of R1, R2, and R3 and to σ* (Taft's polar parameter) of R3 was formulated. The general picture of ligand interactions with chymotrypsin as seen with correlation analysis is discussed. © 1979.