A light-activated antibody catalyst

Jari Yli-Kauhaluoma, Matthew Taylor, Timothy Hoffman, Richard Lerner, Kim Janda

Research output: Contribution to journalArticleScientificpeer-review

26 Citations (Scopus)

Abstract

A catalytic antibody for a multistep Norrish type II photochemical reaction was investigated. Absorption of light energy by α-ketoamide substrate 1b produced a high-energy biradical intermediate, that was then directed by the antibody microenvironment to form tetrahydropyrazine 13 with a kcat of 1.4 × 10-3 min-1 at 280 nm irradiation and an enantiomeric excess of 78%. Antibody-catalyzed reactions performed with radiolabeled substrate indicated that little self-inactivation (6.8 mol % covalent modification after four turnovers per antibody) occurred.
The singular product obtained in the antibody-catalyzed reaction was not observed in the uncatalyzed reaction unless the pH was lowered below 4. Studies suggested that the interplay of conformational control and chemical catalysis were responsible for the high specificity. A change in protonation state of the antibody was correlated with the inclusion of a new reaction pathway in the antibody-catalyzed reaction, indicating that general-base catalysis was involved in the rerouting of the Norrish reaction to form 13. An X-ray crystal structure of the substrate was obtained and suggested that the antibody binds the α-ketoamide in a twisted conformation optimal for the first step of the photochemical reaction.
The antibody described here is a model for the evolution of light-activated enzymes and can serve as a foundation for the development of light-dependent antibody catalysts for a range of even more complex photochemical reactions.
Original languageEnglish
Pages (from-to)12783-12790
JournalJournal of the American Chemical Society
Volume120
Issue number49
DOIs
Publication statusPublished - 1998
MoE publication typeA1 Journal article-refereed

Fingerprint

Antibodies
Light
Catalysts
Photochemical reactions
Catalysis
Substrates
Catalytic Antibodies
Protonation
Conformations
Enzymes
Crystal structure
X-Rays
Irradiation
X rays

Cite this

Yli-Kauhaluoma, J., Taylor, M., Hoffman, T., Lerner, R., & Janda, K. (1998). A light-activated antibody catalyst. Journal of the American Chemical Society, 120(49), 12783-12790. https://doi.org/10.1021/ja982711r
Yli-Kauhaluoma, Jari ; Taylor, Matthew ; Hoffman, Timothy ; Lerner, Richard ; Janda, Kim. / A light-activated antibody catalyst. In: Journal of the American Chemical Society. 1998 ; Vol. 120, No. 49. pp. 12783-12790.
@article{f2436d29121c4f83b1f9dad314d73fe1,
title = "A light-activated antibody catalyst",
abstract = "A catalytic antibody for a multistep Norrish type II photochemical reaction was investigated. Absorption of light energy by α-ketoamide substrate 1b produced a high-energy biradical intermediate, that was then directed by the antibody microenvironment to form tetrahydropyrazine 13 with a kcat of 1.4 × 10-3 min-1 at 280 nm irradiation and an enantiomeric excess of 78{\%}. Antibody-catalyzed reactions performed with radiolabeled substrate indicated that little self-inactivation (6.8 mol {\%} covalent modification after four turnovers per antibody) occurred. The singular product obtained in the antibody-catalyzed reaction was not observed in the uncatalyzed reaction unless the pH was lowered below 4. Studies suggested that the interplay of conformational control and chemical catalysis were responsible for the high specificity. A change in protonation state of the antibody was correlated with the inclusion of a new reaction pathway in the antibody-catalyzed reaction, indicating that general-base catalysis was involved in the rerouting of the Norrish reaction to form 13. An X-ray crystal structure of the substrate was obtained and suggested that the antibody binds the α-ketoamide in a twisted conformation optimal for the first step of the photochemical reaction. The antibody described here is a model for the evolution of light-activated enzymes and can serve as a foundation for the development of light-dependent antibody catalysts for a range of even more complex photochemical reactions.",
author = "Jari Yli-Kauhaluoma and Matthew Taylor and Timothy Hoffman and Richard Lerner and Kim Janda",
year = "1998",
doi = "10.1021/ja982711r",
language = "English",
volume = "120",
pages = "12783--12790",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society ACS",
number = "49",

}

Yli-Kauhaluoma, J, Taylor, M, Hoffman, T, Lerner, R & Janda, K 1998, 'A light-activated antibody catalyst', Journal of the American Chemical Society, vol. 120, no. 49, pp. 12783-12790. https://doi.org/10.1021/ja982711r

A light-activated antibody catalyst. / Yli-Kauhaluoma, Jari; Taylor, Matthew; Hoffman, Timothy; Lerner, Richard; Janda, Kim.

In: Journal of the American Chemical Society, Vol. 120, No. 49, 1998, p. 12783-12790.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - A light-activated antibody catalyst

AU - Yli-Kauhaluoma, Jari

AU - Taylor, Matthew

AU - Hoffman, Timothy

AU - Lerner, Richard

AU - Janda, Kim

PY - 1998

Y1 - 1998

N2 - A catalytic antibody for a multistep Norrish type II photochemical reaction was investigated. Absorption of light energy by α-ketoamide substrate 1b produced a high-energy biradical intermediate, that was then directed by the antibody microenvironment to form tetrahydropyrazine 13 with a kcat of 1.4 × 10-3 min-1 at 280 nm irradiation and an enantiomeric excess of 78%. Antibody-catalyzed reactions performed with radiolabeled substrate indicated that little self-inactivation (6.8 mol % covalent modification after four turnovers per antibody) occurred. The singular product obtained in the antibody-catalyzed reaction was not observed in the uncatalyzed reaction unless the pH was lowered below 4. Studies suggested that the interplay of conformational control and chemical catalysis were responsible for the high specificity. A change in protonation state of the antibody was correlated with the inclusion of a new reaction pathway in the antibody-catalyzed reaction, indicating that general-base catalysis was involved in the rerouting of the Norrish reaction to form 13. An X-ray crystal structure of the substrate was obtained and suggested that the antibody binds the α-ketoamide in a twisted conformation optimal for the first step of the photochemical reaction. The antibody described here is a model for the evolution of light-activated enzymes and can serve as a foundation for the development of light-dependent antibody catalysts for a range of even more complex photochemical reactions.

AB - A catalytic antibody for a multistep Norrish type II photochemical reaction was investigated. Absorption of light energy by α-ketoamide substrate 1b produced a high-energy biradical intermediate, that was then directed by the antibody microenvironment to form tetrahydropyrazine 13 with a kcat of 1.4 × 10-3 min-1 at 280 nm irradiation and an enantiomeric excess of 78%. Antibody-catalyzed reactions performed with radiolabeled substrate indicated that little self-inactivation (6.8 mol % covalent modification after four turnovers per antibody) occurred. The singular product obtained in the antibody-catalyzed reaction was not observed in the uncatalyzed reaction unless the pH was lowered below 4. Studies suggested that the interplay of conformational control and chemical catalysis were responsible for the high specificity. A change in protonation state of the antibody was correlated with the inclusion of a new reaction pathway in the antibody-catalyzed reaction, indicating that general-base catalysis was involved in the rerouting of the Norrish reaction to form 13. An X-ray crystal structure of the substrate was obtained and suggested that the antibody binds the α-ketoamide in a twisted conformation optimal for the first step of the photochemical reaction. The antibody described here is a model for the evolution of light-activated enzymes and can serve as a foundation for the development of light-dependent antibody catalysts for a range of even more complex photochemical reactions.

U2 - 10.1021/ja982711r

DO - 10.1021/ja982711r

M3 - Article

VL - 120

SP - 12783

EP - 12790

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 49

ER -

Yli-Kauhaluoma J, Taylor M, Hoffman T, Lerner R, Janda K. A light-activated antibody catalyst. Journal of the American Chemical Society. 1998;120(49):12783-12790. https://doi.org/10.1021/ja982711r