Design, Synthesis, and Evaluation of Small Molecules as Potential Inhibitors of Bacterial Cell Wall Biosynthesis

Master's Thesis

Abstract

Since the use of penicillin during World War II, the cell wall biosynthesis pathway has been a target for antibiotic treatment. Although hundreds of ÌÄü-lactam antibiotics have been developed and studied at great length, bacterial resistance continually threatens the efficacy with which bacterial infections may be treated. This work investigates small molecule scaffolds as potential inhibitors of the cell wall biosynthesis pathway. The molecules are based on a dipeptide core or were discovered via computational screening of a small molecule library against the active site of a penicillin-binding protein. The small molecules were analyzed for in vivo antibacterial activity utilizing minimum inhibitory concentration determination. In vitro activity was evaluated using established nitrocefin and Bocillin-FL competition assays for DD-transpeptidases. Additionally, an Amplex Red coupled assay was employed to probe DD-carboxypeptidase activity. The design, synthesis, and evaluation of these small molecules are discussed herein.

Attributes

Attribute NameValues
URN
  • etd-06292011-080424

Author Apryle Marie O'Farrell
Advisor Prof. Brian Baker
Contributor Prof. Marvin Miller, Committee Member
Contributor Prof. Patricia Clark, Committee Member
Contributor Prof. Bradley Smith, Committee Member
Contributor Prof. Brian Baker, Committee Chair
Degree Level Master's Thesis
Degree Discipline Chemistry and Biochemistry
Degree Name MS
Defense Date
  • 2011-06-07

Submission Date 2011-06-29
Country
  • United States of America

Subject
  • peptidoglycan

  • penicillin binding proteins

  • PBPs

Publisher
  • University of Notre Dame

Language
  • English

Record Visibility Public
Content License
  • All rights reserved

Departments and Units

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