This website uses cookies so that we can provide you with the best user experience possible. Cookie information is stored in your browser and performs functions such as recognising you when you return to our website and helping our team to understand which sections of the website you find most interesting and useful.
Interactions between Macromolecules and their Ligands in Solution State
Objectives
- to compare the free and bound structures of several macrolides possessing a variety of biological activities
- to identify areas of the macrolide which are the closest to the E. coli ribosome surface and are most likely involved in binding to the active site
Comparison of free and bound structures of macrolides
- Analysis of trNOESY experiments showed that macrolide conformation does not change significantly upon binding to the E. coli ribosome
Comparison of STD signal enhancements and distances from ribosome taken from X-ray structure of co-crystallized azithromycin with H. Marismortui (*peak overlap)
STD NMR as a tool
- Competition experiment has proved the examined macrolide binds to the active site
- STD enhancements observed for azithromycin and distances between azithromycin and ribosome (determined in X-ray co-crystallized structure of azithromycin and H. marismortui) showed a good correlation
- STD NMR can be used as a tool to monitor the interactions between macrolides and ribosome
Epitope mapping
Macrolides have three distinct areas which are the closest to the ribosome:
- methyl group 15 (macrocyclic ring)
- 3”Me and 3”OMe (cladinose)
- dimethylamino group (desosamine)
References
- P. Novak, J. Barber, A. Čikoš, B. Arsic, J. Plavec, G. Lazarevski, P. Tepeš and N. Košutić-Hulita,
Free and bound state structures of 6-O-methyl homoerythromycins and epitope mapping of their interactions with ribosomes
Bioorg Med Chem 2009, 17, 5857-5867