Substrate attenuation: An approach to improve antibody catalysis

Kim D. Janda; Stephen J. Benkovic; Donald A. McLeod; Diane M. Schloeder; Richard A. Lerner

doi:10.1016/S0040-4020(01)81784-1

Substrate attenuation: An approach to improve antibody catalysis

Kim D. Janda, Stephen J. Benkovic, Donald A. McLeod, Diane M. Schloeder, Richard A. Lerner

Chemistry

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

Antibodies raised to quinaldine phosphonamide 1a showed no ability to hydrolyze its most homologous substrates amide and ester 2 and 3, respectively. However, within this same set of antibodies some thirteen showed a great propensity to hydrolyse a structurally similar naphthyl ester. In addition to heteroatom discrimination one of the antibodies examined in detail displayed an increase in catalytic efficiency presumably via weak apparent binding (K_m) when phenylesters were employed as substrates. These findings suggest abzyme catalysis may be improved via substrate attenuation. Antibodies raised to quinaldine phosphonamide 1a showed no ability to hydrolyze its most homologous substrates amide and ester 2 and 3, respectively. However, within this same set of antibodies some thirteen showed a great propensity to hydrolyse a structurally similar naphthyl ester. In addition to heteroatom discrimination one of the antibodies examined in detail displayed an increase in catalytic efficiency presumably via weak apparent binding (K_m) when phenylesters were employed as substrates. These findings suggest abzyme catalysis may be improved via substrate attenuation.

Original language	English (US)
Pages (from-to)	2503-2506
Number of pages	4
Journal	Tetrahedron
Volume	47
Issue number	14-15
DOIs	https://doi.org/10.1016/S0040-4020(01)81784-1
State	Published - 1991

All Science Journal Classification (ASJC) codes

Biochemistry
Drug Discovery
Organic Chemistry

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title = "Substrate attenuation: An approach to improve antibody catalysis",

abstract = "Antibodies raised to quinaldine phosphonamide 1a showed no ability to hydrolyze its most homologous substrates amide and ester 2 and 3, respectively. However, within this same set of antibodies some thirteen showed a great propensity to hydrolyse a structurally similar naphthyl ester. In addition to heteroatom discrimination one of the antibodies examined in detail displayed an increase in catalytic efficiency presumably via weak apparent binding (Km) when phenylesters were employed as substrates. These findings suggest abzyme catalysis may be improved via substrate attenuation. Antibodies raised to quinaldine phosphonamide 1a showed no ability to hydrolyze its most homologous substrates amide and ester 2 and 3, respectively. However, within this same set of antibodies some thirteen showed a great propensity to hydrolyse a structurally similar naphthyl ester. In addition to heteroatom discrimination one of the antibodies examined in detail displayed an increase in catalytic efficiency presumably via weak apparent binding (Km) when phenylesters were employed as substrates. These findings suggest abzyme catalysis may be improved via substrate attenuation.",

author = "Janda, {Kim D.} and Benkovic, {Stephen J.} and McLeod, {Donald A.} and Schloeder, {Diane M.} and Lerner, {Richard A.}",

note = "Funding Information: ACKNOWLEDGMENT. This researchw as supportedin part by a grant from the National Instituteo f 43858)t o KDJ. The authorsw ish to thankM rs MatthewF oley for the preparationo f the manuscript",

year = "1991",

doi = "10.1016/S0040-4020(01)81784-1",

language = "English (US)",

volume = "47",

pages = "2503--2506",

journal = "Tetrahedron",

issn = "0040-4020",

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number = "14-15",

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TY - JOUR

T1 - Substrate attenuation

T2 - An approach to improve antibody catalysis

AU - Janda, Kim D.

AU - Benkovic, Stephen J.

AU - McLeod, Donald A.

AU - Schloeder, Diane M.

AU - Lerner, Richard A.

N1 - Funding Information: ACKNOWLEDGMENT. This researchw as supportedin part by a grant from the National Instituteo f 43858)t o KDJ. The authorsw ish to thankM rs MatthewF oley for the preparationo f the manuscript

PY - 1991

Y1 - 1991

N2 - Antibodies raised to quinaldine phosphonamide 1a showed no ability to hydrolyze its most homologous substrates amide and ester 2 and 3, respectively. However, within this same set of antibodies some thirteen showed a great propensity to hydrolyse a structurally similar naphthyl ester. In addition to heteroatom discrimination one of the antibodies examined in detail displayed an increase in catalytic efficiency presumably via weak apparent binding (Km) when phenylesters were employed as substrates. These findings suggest abzyme catalysis may be improved via substrate attenuation. Antibodies raised to quinaldine phosphonamide 1a showed no ability to hydrolyze its most homologous substrates amide and ester 2 and 3, respectively. However, within this same set of antibodies some thirteen showed a great propensity to hydrolyse a structurally similar naphthyl ester. In addition to heteroatom discrimination one of the antibodies examined in detail displayed an increase in catalytic efficiency presumably via weak apparent binding (Km) when phenylesters were employed as substrates. These findings suggest abzyme catalysis may be improved via substrate attenuation.

AB - Antibodies raised to quinaldine phosphonamide 1a showed no ability to hydrolyze its most homologous substrates amide and ester 2 and 3, respectively. However, within this same set of antibodies some thirteen showed a great propensity to hydrolyse a structurally similar naphthyl ester. In addition to heteroatom discrimination one of the antibodies examined in detail displayed an increase in catalytic efficiency presumably via weak apparent binding (Km) when phenylesters were employed as substrates. These findings suggest abzyme catalysis may be improved via substrate attenuation. Antibodies raised to quinaldine phosphonamide 1a showed no ability to hydrolyze its most homologous substrates amide and ester 2 and 3, respectively. However, within this same set of antibodies some thirteen showed a great propensity to hydrolyse a structurally similar naphthyl ester. In addition to heteroatom discrimination one of the antibodies examined in detail displayed an increase in catalytic efficiency presumably via weak apparent binding (Km) when phenylesters were employed as substrates. These findings suggest abzyme catalysis may be improved via substrate attenuation.

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EP - 2506

JO - Tetrahedron

JF - Tetrahedron

IS - 14-15

ER -

Substrate attenuation: An approach to improve antibody catalysis

Abstract

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