The structure of erythromycin enol ether as a model for its activity as a motilide.
Erythromycin enol ether is a potent mimic of the peptide hormone motilin. To understand its biological activity, its three-dimensional structure in CD(2)Cl(2) was determined from constrained molecular mechanics using constraints derived from NMR spectra. The structure of the enol ether is well defined by 10 structures that minimize the energy and satisfy the NMR data. We infer the molecular basis for its activity as a motilide from a comparison of its structure with that of motilin. The macrolide ring of the enol ether is a beta-turn mimic of the peptide. Furthermore, a superposition of the structures of the enol ether and motilin shows a striking overlap of the sugar rings attached to the macrolide ring with essential aromatic side chains in the peptide.
Steinmetz
Wayne E
WE
Chemistry Department, Pomona College, Claremont, California 91711-6338, USA. wsteinmetz@pomona.edu
Shapiro
Brett L
BL
Roberts
John J
JJ
D004917:Erythromycin / Q000031:analogs & derivatives / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D018716:Molecular Mimicry; D009037:Motilin / Q000737:chemistry*; D017433:Protein Structure, Secondary
C093673:8,9-anhydroerythromycin A 6,9-hemiketal; D009037:Motilin; D004917:Erythromycin