Molecular Modeling in Drug Design for the Development of Organophosphorus Antidotes/Prophylactics.
Abstract
Organophosphorus poisons consist of substituted phosphoric or phosphoric acids, coupled to a labile 'leaving' group. They react with acetylcholinesterases with expulsion of the leaving group and acylation of a key serine residue at the active site of the enzyme, a process which leads to inactivation of the enzyme and which is essentially irreversible under physiological conditions. Some of the approaches proposed to alleviate this problem are: 1) removal of the offending phosphorus residue, regenerating intact cholinesterase, 2) prior blockade of the active site with a less toxic, reversible agent, and 3) amelioration of the effects of excess acetyl choline by blockade of its receptor sites. This problem has been studied using computer-assisted techniques.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1986
- Accession Number
- ADA176374
Entities
People
- R. Venkataraghavan