The antibiotic moenomycin A inhibits the biosynthesis of peptidoglycan, the main structural polymer of the bacterial cell wall. The inhibition is based on a reversible binding of the antibiotic to one of the substrate binding sites in enzymes such as penicillin-binding protein (PBP) 1b. A novel assay based on surface plasmon resonance (SPR) has been established that can be used to investigate selective binding of the moenomycin sugar moiety and other transglycosylase inhibitors to this enzyme. Suitable ligands were prepared from moenomycin A and coupled to SPR sensor surfaces. Moenomycin analogues with structural variations were used to perform competitive SPR experiments with PBP 1b. The SPR results confirm for the first time that the trisaccharide fragment of moenomycin A (C-E-F-G-H-I) is the minimal structure that possesses all moieties sufficient for biological activity and for affinity towards PBP 1b. The method seems to be appropriate for use in screens for transglycosylase inhibitors that bind to the moenomycin-binding site of the enzyme.

The anchoring of moenomycin A (1) to the bacterial cell cytoplasmic membrane is essential for its biological activity. The first details of the strength of this interaction and the kinetics of the diffusion-mediated intervesicle transfer have been obtained by means of fluorescence spectroscopic methods using a coumarin-labeled moenomycin A derivative.

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The antibiotic moenomycin A inhibits the biosynthesis of peptidoglycan, the main structural polymer of the bacterial cell wall. The inhibition is based on a reversible binding of the antibiotic to one of the substrate binding sites at enzymes such as the penicillin binding protein 1b (PBP 1b). This binding has been employed to isolate PBP 1b by affinity chromatography. Suitable ligands have been prepared from moenomycin A and coupled both to affinity supports and to surface plasmon resonance sensor surfaces. The reactions that take place upon immobilization of the ligands to the affinity support and the sensor surface, respectively, have been studied in detail. With the help of surface plasmon resonance the optimal conditions for binding of PBP 1b to moenomycin-derivated ligands have been established. For the first time the selective binding of the moenomycin sugar moiety to the enzyme has been demonstrated.