Ion binding of penicillins to proteins

Abstract

1. 1. A new method is described, utilising the reactions of hydrated electrons ( e aq −), to demonstrate that reversible ion binding occurs between a series of penicillins and the proteins, bovine serum albumin and lysozyme. 2. 2. The structure of the penicillin side chain considerably influences the binding process with bovine serum albumin. The first molecular of benzyl or phenoxymethyl penicillin which binds results in a greater decrease in the reactivity of the protein towards e aq − than subsequent molecules. 6-Aminopenicillanic acid, however, exerts an opposite effect and initially increases the reactivity of bovine serum albumin towards e aq −. Methyl penicillin and ampicillin binding decreases bovine serum albumin reactivity linearly with penicillin concentration. If the free carboxylic group is protected as in methyl and acetoxymethyl esters of benzyl penicillin no such ion binding is observed. The results are discussed in terms of the types of binding possible between these penicillins and bovine serum albumin. 3. 3. Six penicillin molecules only can bind to lysozyme and our results indicate that these are associated with the lysine residues. 4. 4. The protein-penicillin complex can be dissociated with salt. Complete breakdown of the benzyl penicillin complex with bovine serum albumin is achieved at approx. 1 · 10 −3 M KCl, but to dissociate the lysozyme complex approx. 1 · 10 −2rmM KCl is required.