PMID- 12204689
OWN - NLM
STAT- MEDLINE
DCOM- 20030606
LR  - 20191025
IS  - 1074-5521 (Print)
IS  - 1074-5521 (Linking)
VI  - 9
IP  - 8
DP  - 2002 Aug
TI  - Functional analysis of the lipoglycodepsipeptide antibiotic ramoplanin.
PG  - 897-906
AB  - 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.
FAU - Cudic, Predrag
AU  - Cudic P
AD  - Johnson Research Foundation, Department of Biochemistry and Biophysics, 
      Philadelphia, PA 19104, USA.
FAU - Behenna, Douglas C
AU  - Behenna DC
FAU - Kranz, James K
AU  - Kranz JK
FAU - Kruger, Ryan G
AU  - Kruger RG
FAU - Wand, A Joshua
AU  - Wand AJ
FAU - Veklich, Yuri I
AU  - Veklich YI
FAU - Weisel, John W
AU  - Weisel JW
FAU - McCafferty, Dewey G
AU  - McCafferty DG
LA  - eng
GR  - DK39806/DK/NIDDK NIH HHS/United States
GR  - GM20206/GM/NIGMS NIH HHS/United States
GR  - AI46611/AI/NIAID NIH HHS/United States
GR  - HL30954/HL/NHLBI NIH HHS/United States
GR  - R01 AI046611/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Chem Biol
JT  - Chemistry & biology
JID - 9500160
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Depsipeptides)
RN  - 0 (Peptides, Cyclic)
RN  - 0 (Peptidoglycan)
RN  - 0WX9996O2G (ramoplanin)
RN  - E524N2IXA3 (Ornithine)
SB  - IM
MH  - Anti-Bacterial Agents/*chemistry/pharmacology
MH  - *Depsipeptides
MH  - Dimerization
MH  - Drug Design
MH  - Drug Stability
MH  - Glycosylation
MH  - Molecular Conformation
MH  - Ornithine
MH  - Peptides, Cyclic/*chemistry/pharmacology
MH  - Peptidoglycan/biosynthesis/drug effects/metabolism
MH  - Structure-Activity Relationship
EDAT- 2002/09/03 10:00
MHDA- 2003/06/07 05:00
CRDT- 2002/09/03 10:00
PHST- 2002/09/03 10:00 [pubmed]
PHST- 2003/06/07 05:00 [medline]
PHST- 2002/09/03 10:00 [entrez]
AID - S1074552102001916 [pii]
AID - 10.1016/s1074-5521(02)00191-6 [doi]
PST - ppublish
SO  - Chem Biol. 2002 Aug;9(8):897-906. doi: 10.1016/s1074-5521(02)00191-6.