A quant. structure-reactivity relationship for the Michael-type addn. of thiols onto acrylates was detd. Several thiol-contg. peptides were investigated by examg. the correlation between the second-order rate const. of their addn. onto PEG-diacrylate and the pKa of the thiols within a peptide. By introducing charged amino acids in close proximity to a cysteine, the pKa of the thiol was systematically modulated by electrostatic interactions. Pos. charges from the amino acid arginine decreased the pKa of the thiol and accelerated the reaction with acrylates while neg. charges from aspartic acids showed the opposite effect. A linear correlation between thiolate concns. and kinetic consts. was found, confirming the role of thiolates as the reactive species in this Michael-type reaction. The relevant factors influencing the reactivity were the sign and the no. of the neighboring charges, while the position of these charges had little effect on reactivity. These results provide a basis for the rational design of peptides, where the kinetics, and thus, selectivity of protein/peptide conjugation with polymeric structures via Michael-type addn. reactions can be controlled. [on SciFinder (R)]