Degradation and reconstruction of moenomycin A and derivatives: dissecting the function of the isoprenoid chain.

Masaatsu Adachi, Yi Zhang, Catherine Leimkuhler, Binyuan Sun, John V LaTour, Daniel E Kahne

Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.

Journal of the American Chemical Society 2006 Nov 1

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Moenomycin A is the only known natural product that inhibits peptidoglycan biosynthesis by bind ing the bacterial transglycosylases. We describe a degradation/reconstruction route to manipulate the reducing end of moenomycin A. A comparison of the biological and enzyme inhibitory activity of moenomycin A and an analogue containing a nerol lipid in place of the natural C25 lipid chain provides insight into the role of the moenocinol unit. Our results show that a lipid chain having ten carbons in moenocinol is sufficient for enzyme inhibition, but a longer chain is required for biological acitivity, apparently because the molecule must partition into biological membranes to reach its target in bacterial cells.

Citation

Masaatsu Adachi, Yi Zhang, Catherine Leimkuhler, Binyuan Sun, John V LaTour, Daniel E Kahne. Degradation and reconstruction of moenomycin A and derivatives: dissecting the function of the isoprenoid chain. Journal of the American Chemical Society. 2006 Nov 1;128(43):14012-3