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Functional analysis of the lipoglycodepsipeptide antibiotic ramoplanin.

Publication ,  Journal Article
Cudic, P; Behenna, DC; Kranz, JK; Kruger, RG; Wand, AJ; Veklich, YI; Weisel, JW; McCafferty, DG
Published in: Chemistry & biology
August 2002

The peptide antibiotic ramoplanin is highly effective against several drug-resistant gram-positive bacteria, including vancomycin-resistant Enterococcus faecium (VRE) and methicillin-resistant Staphylococcus aureus (MRSA), two important opportunistic human pathogens. Ramoplanin inhibits bacterial peptidoglycan (PG) biosynthesis by binding to Lipid intermediates I and II at a location different than the N-acyl-D-Ala-D-Ala dipeptide site targeted by vancomycin. Lipid I/II capture physically occludes these substrates from proper utilization by the late-stage PG biosynthesis enzymes MurG and the transglycosylases. Key structural features of ramoplanin responsible for antibiotic activity and PG molecular recognition have been discovered by antibiotic semisynthetic modification in conjunction with NMR analyses. These results help define a minimalist ramoplanin pharmacophore and introduce the possibility of generating ramoplanin-derived peptide or peptidomimetic antibiotics for use against VRE, MRSA, and related pathogens.

Duke Scholars

Published In

Chemistry & biology

DOI

EISSN

1879-1301

ISSN

1074-5521

Publication Date

August 2002

Volume

9

Issue

8

Start / End Page

897 / 906

Related Subject Headings

  • Structure-Activity Relationship
  • Peptidoglycan
  • Peptides, Cyclic
  • Ornithine
  • Organic Chemistry
  • Molecular Conformation
  • Glycosylation
  • Drug Stability
  • Drug Design
  • Dimerization
 

Citation

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Cudic, P., Behenna, D. C., Kranz, J. K., Kruger, R. G., Wand, A. J., Veklich, Y. I., … McCafferty, D. G. (2002). Functional analysis of the lipoglycodepsipeptide antibiotic ramoplanin. Chemistry & Biology, 9(8), 897–906. https://doi.org/10.1016/s1074-5521(02)00191-6
Cudic, Predrag, Douglas C. Behenna, James K. Kranz, Ryan G. Kruger, A Joshua Wand, Yuri I. Veklich, John W. Weisel, and Dewey G. McCafferty. “Functional analysis of the lipoglycodepsipeptide antibiotic ramoplanin.Chemistry & Biology 9, no. 8 (August 2002): 897–906. https://doi.org/10.1016/s1074-5521(02)00191-6.
Cudic P, Behenna DC, Kranz JK, Kruger RG, Wand AJ, Veklich YI, et al. Functional analysis of the lipoglycodepsipeptide antibiotic ramoplanin. Chemistry & biology. 2002 Aug;9(8):897–906.
Cudic, Predrag, et al. “Functional analysis of the lipoglycodepsipeptide antibiotic ramoplanin.Chemistry & Biology, vol. 9, no. 8, Aug. 2002, pp. 897–906. Epmc, doi:10.1016/s1074-5521(02)00191-6.
Cudic P, Behenna DC, Kranz JK, Kruger RG, Wand AJ, Veklich YI, Weisel JW, McCafferty DG. Functional analysis of the lipoglycodepsipeptide antibiotic ramoplanin. Chemistry & biology. 2002 Aug;9(8):897–906.

Published In

Chemistry & biology

DOI

EISSN

1879-1301

ISSN

1074-5521

Publication Date

August 2002

Volume

9

Issue

8

Start / End Page

897 / 906

Related Subject Headings

  • Structure-Activity Relationship
  • Peptidoglycan
  • Peptides, Cyclic
  • Ornithine
  • Organic Chemistry
  • Molecular Conformation
  • Glycosylation
  • Drug Stability
  • Drug Design
  • Dimerization