Tripeptide substrate

Since MurD was the primary target, it was made the rate-limiting step in the coupled enzyme assay and conditions were optimized for that catalytic reaction. The kinetic parameters were determined for MurD. The Km for UMA and d-G1u guided the choice of substrate concentrations for the MurD reaction so the enzyme was optimally efficient [31], The kinetic parameters for the amino acid or dipeptide and tripeptide substrates for MurE and MurF were then determined... 

The synthesis of ketomethylene pseudopeptide analogues was accomplished by L. Cheng et al., and their biological activity as thrombin inhibitors was tested. These analogues were prepared through a modified Dakin-West reaction under mild conditions and in almost quantitative yield. The required anhydride was prepared from monomethyl succinate, and a large excess of it was mixed with the tripeptide substrate in pyridine in addition to triethylamine and catalytic amounts of DMAP. The reaction mixture was heated for one hour at 40-50 °C. 

Strictly speaking, once IPNS has operated on a tripeptide substrate, any further changes are outside the domain of peptide chemistry and biochemistry and hence of this book. Nevertheless, for the sake of completeness the conversion of penicillins into cephalosporins is briefly mentioned. It has been mentioned above that the production of a cephalosporin may accompany the formation of a penicillin. This can occur, for example, if an extract of Cephalosporium acremonium is used as a source of IPNS. It has been shown that the formation of a cephalosporin results from a ring expansion of a penicillin. Thus penicillin N can be converted into the cephalosporin (8.44), which is also an antibiotic. 

Evans, G. O. 1989. Species relationships for plasma angiotensin converting enzyme activity using a furanacryloyl tripeptide substrate. Experimental Animals 38 897-898. 

To a much smaller extent non-enzymic processes have also been used to catalyse the stereoselective acylation of alcohols. For example, a simple tripeptide has been used, in conjunction with acetic anhydride, to convert rram-2-acctylaminocyclohexanol into the (K),(R)-Qster and recovered (S),(S)-alcohol[17]. In another, related, example a chiral amine, in the presence of molecular sieve and the appropriate acylating agent, has been used as a catalyst in the conversion of cyclohexane-1(S), 2(/ )-diol into 2(S)-benzoyloxy-cyclohexan-1 f / j-ol1 IS]. Such alternative methods have not been extensively explored, though reports by Fu, Miller, Vedejs and co-workers on enantioselective esterifications, for example of 1-phenylethanol and other substrates using /. vo-propyl anhydride and a chiral phosphine catalyst will undoubtedly attract more attention to this area1191. 

There have been sustained efforts in recent years to use the carrier systems of the brush-border membrane of intestinal mucosa to increase absorption of orally administered drugs [29] [30]. One system of particular interest is the intestinal peptide carrier (hPEPTl) whose physiological function is the absorption of di- and tripeptides and whose xenobiotic substrates include /3-lactam antibiotics, renin inhibitors, and angiotensin-converting enzyme (ACE) inhibitors [31]. 

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