Kinetics of Reactions Involved in Penicillin Allergy I: Mechanism of Reaction of Penicillins and 6-Aminopenicillanic Acid with Glycine in Alkaline Solution

The principal antigenic determinant of penicillin allergy, penicilloyl-protein, may be formed either by direct reaction of penicillin with protein, or through penicillenic acid, a rearrangement product of penicillin. As part of a study of the mechanism of the direct reaction, the kinetics of reaction of glycine with a series of penicillins and 6-aminopenicillanic acid has been investigated. The aminolysis of penicillins by glycine is general base catalyzed, while the reaction with 6-APA is uncatalyzed. The latter is probably due to intramolecular general-base catalysis. The rates of reaction with glycine of all the penicillins studied are of the same order of magnitude. This is in contrast to the rates of penicillenic acid formation which are highly dependent upon the nature of the penicillin side chain. The pertinence of these results to the mechanism of formation of penicillin antigen is discussed.