Alanine Scan of [l-Dap2]Ramoplanin A2 Aglycon: Assessment of the Importance of Each Residue
- 26 June 2007
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 129 (28), 8747-8755
- https://doi.org/10.1021/ja068573k
Abstract
In efforts that define the importance of each residue and that identify key regions of the molecule, an alanine scan of the ramoplanin A2 aglycon, a potent antibiotic that inhibits bacterial cell wall biosynthesis, is detailed. As a consequence of both its increased stability (lactam vs lactone) and its “relative” ease of synthesis, the alanine scan was conducted on [Dap2]ramoplanin A2 aglycon, which possesses antimicrobial activity equal to or slightly more potent than that of ramoplanin A2 or its aglycon. Thus, 14 key analogues of the ramoplanin A2 aglycon, representing a scan of residues 3−13, 15, and 17, were prepared enlisting a convergent solution-phase total synthesis that consolidated the effort to a manageable level. The antimicrobial activity of the resulting library of analogues provides insight into the importance and potential role of each residue of this complex glycopeptide antibiotic.Keywords
This publication has 47 references indexed in Scilit:
- Structure elucidation and 3D solution conformation of the antibiotic enduracidin determined by NMR spectroscopy and molecular dynamicsMagnetic Resonance in Chemistry, 2005
- Dissecting Ramoplanin: Mechanistic Analysis of Synthetic Ramoplanin Analogues as a Guide to the Design of Improved AntibioticsJournal of the American Chemical Society, 2004
- Ramoplanin: a novel antimicrobial agent with the potential to prevent vancomycin-resistant enterococcal infection in high-risk patientsJournal of Antimicrobial Chemotherapy, 2003
- The Lantibiotic Mersacidin Inhibits Peptidoglycan Biosynthesis at the Level of TransglycosylationEuropean Journal of Biochemistry, 1997
- Retention of native‐like structure in an acyclic counterpart of a β‐sheet antibioticFEBS Letters, 1993
- In vitro evaluation of ramoplanin (A16686 or MDL62198): A new depsipeptide complex for potential topical useDiagnostic Microbiology and Infectious Disease, 1989
- The role of the chlorine substituents in the antibiotic vancomycin: preparation and characterization of mono- and didechlorovancomycinJournal of the American Chemical Society, 1985
- Practical synthesis of cyclic peptides, with an example of dependence of cyclization yield upon linear sequenceThe Journal of Organic Chemistry, 1979
- Enduracidin, a New Antibiotic. VIII. Structures of Enduracidins A and BCHEMICAL & PHARMACEUTICAL BULLETIN, 1973
- Enduracidin, a New Antibiotic. VII. Primary Structure of the Peptide MoietyCHEMICAL & PHARMACEUTICAL BULLETIN, 1973