# BETA-LACTAMASES -- ACTIVE SITE CHEMISTRY

> **NIH NIH R01** · WESLEYAN UNIVERSITY · 1993 · $129,355

## Abstract

Bacterial resistance to beta-lactam antibiotics continues to become more
prevalent and more clinically important.  It is likely, however, that a
large part of the resistance can be understood and investigated
experimentally in terms of the chemistry of the interactions of beta-
lactamases on one hand, which catalyse the hydrolysis of the antibodies,
and the D-alanyl-D-alanine transpeptidase/-carboxypeptidases on the other,
which catalyse the synthesis and maintenance of the peptide cross-links of
bacterial cell walls, and which are inhibited by beta-lactam antibiotics.
There is now good reason to believe that all of these beta-lactam binding
sites have much in common.  An understanding of the structure and function
of these sites and of the relationship between them is fundamental to
future antibiotics design -- both beta-lactam and otherwise.  The object of
the proposed research is to explore further the chemical functionality and
the substrate binding properties of a series of these active sites, using a
number of modified substrates, novel inhibitors, and potential effectors.
In particular, a novel series of acyclic substrates and derived inhibitors
will be employed.  A mechanistic study of these sites, designed to
determine the role of the functional groups present and the relationship
between the mechanism of action of these enzymes and that of other more
closely studied enzymes, e.g. serine proteinases, will also be commenced.
These studies should lead to a more useful picture of beta-lactamase active
sites, to a better idea as to their relationship to D-alanyl-D-alanine
transpeptidase sites, and thus to new directions or antibiotic development.

## Key facts

- **NIH application ID:** 3127599
- **Project number:** 5R01AI017986-12
- **Recipient organization:** WESLEYAN UNIVERSITY
- **SAM.gov UEI:** ZETJL6DKF963
- **Principal Investigator:** REX F PRATT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $129,355
- **Award type:** 5
- **Project period:** 1982-09-30 → 1995-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127599

## Citation

> US National Institutes of Health, RePORTER application 3127599, BETA-LACTAMASES -- ACTIVE SITE CHEMISTRY (5R01AI017986-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127599. Licensed CC0.

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