Engineering of Paraoxonases for Pre- and Post-treatment of Intoxication by a Broad Spectrum of Nerve Agents and Pesticides
Abstract
Project Summary: The long-term objective of this effort is to develop a generic gene shuffling-based technology to rapidly screen libraries of 1010 proteins/peptides encoded by DNA libraries, for identifying biomolecules that can intercept both existing and emerging organophosphate-based chemical warfare nerve agents (CWNA). The tasks to be performed at the Weizmann Institute to achieve the major goals of the Center current year are outlined below: #1. Screening for paraoxon- parathion- malaoxon- malathion- and phorate-hydrolyzing variants. #2. Validation of the hypothesis concerning the structural motifs in PON1 that are involved in association with HDL, improving rePON1 s affinity for HD, and increasing the biological life time of rePON variants. #3. Steered molecular dynamics. Improvement of the modeling of VX into the rePON1 scaffold, and studies of the mechanism of action of PON1 variants on V-type nerve agents Relevance: this technology is envisaged to have the capability to facilitate rapid discovery of pre- and post-treatment therapeutic drugs targeted against existing and emerging pesticides and nerve agent threats, and may shorten the time from emergence of a threat to identification of potential counter-measures to a few days or weeks.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2014
- Accession Number
- ADA607782
Entities
People
- Dan S Tawfik
- Joel L. Sussman
Organizations
- Weizmann Institute of Science