Accession Number : ADA257229


Title :   Catalytic Antibodies for Prophylaxis/Treatment of Cyanide Poisoning


Descriptive Note : Midterm rept. 15 Feb 9190-14 Aug 1991


Corporate Author : RESEARCH TRIANGLE INST (RTI) INST RESEARCH TRIANGLE PARK NC


Personal Author(s) : Cook, C E


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a257229.pdf


Report Date : 09 Oct 1991


Pagination or Media Count : 69


Abstract : The prophylactic administration of a drug capable of reacting quickly with cyanide and removing it from the circulation is one approach to the problem of cyanide intoxication. Alpha, Beta-Unsaturated ketones, esters, nitriles, etc. , undergo 1,4-addition with hydrogen cyanide to form stable compounds. We have investigated the reaction of cyanide with 4-phenyl-3-buten-2-one at 37 deg C and pH 7.4 in aqueous phosphate buffer. Disappearance of 4-phenyl-3-buten-2-one and appearance of the product 4-phenyl-4-cyanobutan-2-one were followed by HPLC analysis on a reverse phase column. The reaction rate was first order in enone and KCN with a rate constant of 0.024 to 0.082 M-lh-1. Catalysis of such reactions by an antibody to the transition state for cyanide addition offers a potential for enhancement of the rate to useful levels. The development of such antibodies by use of transition state analogs as haptens is our overall goal. The antibodies would be combined with a drug which is a substrate for cyanide addition. Design and synthesis of the potential drug and its transition state analog are being carried out.


Descriptors :   *ANTIBODIES , *CATALYSIS , *POISONING , *CYANIDES , BUFFERS , MANAGEMENT , REACTION KINETICS , SYNTHESIS , TOXICITY , AUGMENTATION , RATES , SUBSTRATES , PHASE , HYDROGEN , CONSTANTS , ANALOGS , TRANSITIONS , KINETICS , DRUGS , BUTENES , ESTERS , CIRCULATION , NITRILES , ANTIGENS , PHOSPHATES , KETONES , POTASSIUM COMPOUNDS , APPROACH , INTOXICATION , ADDITION , HYDROGEN CYANIDE


Subject Categories : Toxicology
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE