Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Antibody-catalyzed reversal of chemoselectivity

Academic Article
uri icon
  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Sinha, Subhash
  • Keinan, Ehud
  • Reymond, J. L.

publication date

  • December 1993

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • A monoclonal antibody, 14D9, which has been elicited against a cationic hapten, N-alkyl-N-methyl-3-glutarylamidomethyl piperidinium, in which alkyl = [4-(2-hydroxyethylamido)carbonyl]phenylmethyl, is capable of inverting the intrinsic order of reactivity in a series of structurally related enol ethers and ketals towards hydrolysis. The order of reactivity of compounds 2 (1-methoxy-2-alkylcyclopent-1-ene), 3 (1-methoxy-5-alkylcylopent-1-ene), and 4 (1,1-dimethoxy-2-alkylcyclopentane) has changed from 0.09:0.17:1 in the uncatalyzed reaction to 1100:25:1 under antibody catalysis. Also, the order of reactivity of the three chemically similar ketals, 6a (1-alkyl-2,2-dimethoxypropane), 6b (1-alkyl-1-methyl-2,2-dimethoxypropane), and 4, has changed from 0.23:0.38:1 in the uncatalyzed hydrolysis to 100:9:1 within the antibody active site. As all compounds bind the antibody with very similar affinities, these effects cannot be simply attributed to selective binding by the antibody. In fact, ketal 4, which shows no measurable catalysis, acts as a competitive inhibitor of 14D9-catalyzed hydrolysis of 6a. Both the solution and the antibody-catalyzed hydrolysis of the ketal substrates are shown to be specific acid catalyzed, involving the unimolecular cleavage of the protonated substrate or antibody-substrate complex in the rate-determining step. Reactivity effects from the acid catalyst itself on ketal hydrolysis (reagent-controlled reactivity) are ruled out under this mechanistic scheme.

subject areas

  • Antibodies, Monoclonal
  • Catalysis
  • Cyclopentanes
  • Deuterium Oxide
  • Ethers
  • Haptens
  • Hydrolysis
  • Kinetics
  • Molecular Structure
  • Piperidines
  • Structure-Activity Relationship
  • Substrate Specificity
  • Water
scroll to property group menus

Research

keywords

  • CATALYTIC ANTIBODIES
  • ENOL ETHERS
  • HYDROLYSIS
  • KETALS
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.90.24.11910

PubMed ID

  • 8265647
scroll to property group menus

Additional Document Info

start page

  • 11910

end page

  • 11913

volume

  • 90

issue

  • 24

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support