Phosphorodithioates: synthesis and evaluation of new haptens for the generation of antibody acyl transferases

✍ Scribed by Oliver Brümmer; Paul Wentworth Jr; David P. Weiner; Kim D. Janda

• Publisher: Elsevier Science
• Year: 1999
• Tongue: French
• Weight: 257 KB
• Volume: 40
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(99)01501-4

✦ Synopsis

An extension of the transition state analogue (TSA) hapten approach for the elicitation of catalytic antibodies for acyl-transfer reactions is described. It is based on the enlistment of phosphorodithioate 1 as a stable mimic of the putative tetrahedral intermediate (TI-) formed during the base-catalyzed hydrolysis of bisaryl carbonate 2. Six members of a library of 25 monoclonal antibodies elicited to 1 catalyze the hydrolysis of 2. The most efficient catalyst, 48F10, exhibits Michaelis-Menten kinetics [Km(2)=686 laM, kcat(2)=2.7 min -I, kcat(2)/kuncat(2)=3× 104] and is one of the most active carbonate hydrolyzing antibodies yet reported. This report highlights the utility of haptens that incorporate substitution of the non-bridging phosphorus(V) oxygen atoms present in the more classical TSA approaches with sulfur, to elicit efficient catalysts for acyl-transfer processes.