Second-order rate constants for the hydroxide ion-catalysed hydrolysis of 6-alkyl penicillins are independent of the length of the alkyl side-chain and replacement of the amido by an amino group decreases the susceptibility to nucleophilic attack on 6-aminopenicillanic acid only three-fold. B. cereus β-lactamase I catalyses the hydrolysis of 6-alkyl penicillins with values of kcat/Km which are at least 50-fold greater than that shown by 6-aminopenicillanic acid. For the enzyme-catalysed reaction k cat/Km increases with increasing chain length, reaching a maximum with hexylpenicillin, and then decreases. The binding energy of the alkyl group is weak, only 1.45 kJ mol-1 per methylene residue. Although there appears to be a recognition site for the amido group there is no specific pocket in β-lactamase I for the recognition of hydrophobic residues in the 6-acylamido side-chain of penicillins.
|Number of pages||5|
|Journal||Journal of the Chemical Society, Perkin Transactions 2|
|Publication status||Published - Oct 1988|