Degradation and reconstruction of moenomycin A and derivatives: dissecting the function of the isoprenoid chain.
Moenomycin A is the only known natural product that inhibits peptidoglycan biosynthesis by binding 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.
Adachi
Masaatsu
M
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Zhang
Yi
Y
Leimkuhler
Catherine
C
Sun
Binyuan
B
LaTour
John V
JV
Kahne
Daniel E
DE
D001455:Bambermycins / Q000737:chemistry*; D002240:Carbohydrate Sequence; D006868:Hydrolysis; D008969:Molecular Sequence Data; D013729:Terpenes / Q000737:chemistry*
D013729:Terpenes; D001455:Bambermycins; C437243:moenomycin A