Antibody-catalyzed rearrangement of a peptide bond

Mechanistic and kinetic investigations

Louis J. Liotta, Richard A. Gibbs, Scott D. Taylor, Patricia Ann Benkovic, Stephen Benkovic

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Catalysis of the deamidation of asparagine residues may provide a powerful method for the deactivation of proteins. Catalytic antibodies (Gibbs et al. Science 1992, 258, 803) have been induced that catalyze the deamidation of a model dipeptide through an intermediate succinimide. Investigations of the mechanistic characteristics of two such antibodies, RG2-23C7 and RG2-2E4, revealed their ability to accelerate the hydrolysis of either the R- or S-enantiomers of the succinimide by factors of 10-500-fold to yield differing ratios of the aspartate and isoaspartate products. The mixed product ratios imply that two tetrahedral binding sites of unequal effectiveness were induced in response to the tetrahedral mimics (a phosphinate or secondary hydroxyl) within the hapten structure. The antibody RG2-2E4 also catalyzes the deamidation of either the D- or L-asparagine within the dipeptide through the intermediate cyclic imide, resulting in a multistep reaction sequence featuring a series of tetrahedral transition states. pH-rate profiles do not implicate functional groups within the antibodies' combining sites for either the deamidation or hydrolytic reactions. The strategy of bifunctional or higher order transition state mimics should provide a route to developing catalytic antibodies for reactions requiring multistep processing.

Original languageEnglish (US)
JournalJournal of the American Chemical Society
Volume117
Issue number17
StatePublished - May 3 1995

Fingerprint

Catalytic Antibodies
Antibodies
Peptides
Dipeptides
Asparagine
Kinetics
Isoaspartic Acid
Binding Sites
Imides
Enantiomers
Haptens
Binding sites
Catalysis
Aspartic Acid
Hydroxyl Radical
Functional groups
Hydrolysis
Proteins
Processing
succinimide

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Liotta, L. J., Gibbs, R. A., Taylor, S. D., Benkovic, P. A., & Benkovic, S. (1995). Antibody-catalyzed rearrangement of a peptide bond: Mechanistic and kinetic investigations. Journal of the American Chemical Society, 117(17).
Liotta, Louis J. ; Gibbs, Richard A. ; Taylor, Scott D. ; Benkovic, Patricia Ann ; Benkovic, Stephen. / Antibody-catalyzed rearrangement of a peptide bond : Mechanistic and kinetic investigations. In: Journal of the American Chemical Society. 1995 ; Vol. 117, No. 17.
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Liotta, LJ, Gibbs, RA, Taylor, SD, Benkovic, PA & Benkovic, S 1995, 'Antibody-catalyzed rearrangement of a peptide bond: Mechanistic and kinetic investigations', Journal of the American Chemical Society, vol. 117, no. 17.

Antibody-catalyzed rearrangement of a peptide bond : Mechanistic and kinetic investigations. / Liotta, Louis J.; Gibbs, Richard A.; Taylor, Scott D.; Benkovic, Patricia Ann; Benkovic, Stephen.

In: Journal of the American Chemical Society, Vol. 117, No. 17, 03.05.1995.

Research output: Contribution to journalArticle

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