Page - (000054) - in Biomedical Chemistry: Current Trends and Developments

2. Another acyl substitution reaction involves a second peptide chain that displaces the link to the hydroxyl of a serine residue resulting in the two peptide chains being linked. 1.1.5.3.2 Transpeptidase Inhibition As seen above, the core transformation in the transpeptidase reaction is an acyl substitution reaction. Penicillin (Scheme 1.1.38) is similar to the normal transpeptidase substrates, so it mimics the substrate and binds irreversibly to the enzyme active site. What makes penicillin so effective is that the β-lactam ring is under considerable strain, making the reaction irreversible. The thiazolidine ring further increases the strain by distorting the bonds and removing resonance stabilization. The β-lactam in anionic form is also protected from hydrolysis so the absorption is more efficient. Scheme 1.1.38: Mechanism of the acyl substitution reaction occurring with penicillin and the serine residue from transpeptidase. 1.1.5.3.3. Penicillin Biosynthesis Penicillin biosynthesis begins with the formation of the tripeptide L-δ- (α-aminoadipoyl)-L-cysteinyl-D-valine (ACV) (Scheme 1.1.39) by