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Re-Engineering Vancomycin to Bind D-Ala-D-Lac

English title Re-Engineering Vancomycin to Bind D-Ala-D-Lac
Applicant Stamm Simon
Number 115560
Funding scheme Fellowships for prospective researchers
Research institution The Skaggs Institute for Chemical Biology The Scripps Research Institute
Institution of higher education Institution abroad - IACH
Main discipline Inorganic Chemistry
Start/End 01.01.2007 - 30.06.2008
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Keywords (6)

total synthesis; glycopeptide antibiotics; vancomycin; structure-activity relationships; resistance; antibiotics

Lay Summary (English)

Lay summary
Resistance to antimicrobial agents is increasing at an alarming rate. In particular, the evolution of vancomycin resistance is extremely troublesome, since the glycopeptide antibiotic vancomycin is an antibiotic of last resort, used when other antimicrobial agents are not effective.
Vancomycin resistance is caused by an inducible resistance pathway in which the terminal dipeptide of the nascent peptidoglycan is modified from D-Ala-D-Ala to D-Ala-D-Lac, leading to a reduced binding affinity of the antibiotic to this modified ligand. To counter vancomycin resistance, Dale L. Boger has revealed the origin of this loss in binding affinity and launched a program to re-engineer vancomycin.
The goal of the project is the total synthesis of the thiamidovancomycin aglycon analog. This crucial analog provides both an alternative route to the already described [?[CH2NH]Tpg4] analog by reductive desulfurization, and an advanced intermediate enroute to the highly interesting amidine analog
Direct link to Lay Summary Last update: 21.02.2013

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