Affinity directed reactions of 3-trimethylaminomethyl catechol with the acetylcholine receptor from Torpedo californica

Brian J. Nickoloff; Mark Grimes; Ruth Kelly; Richard A. Hudson

doi:10.1016/S0006-291X(82)80134-4

Affinity directed reactions of 3-trimethylaminomethyl catechol with the acetylcholine receptor from Torpedo californica

Brian J. Nickoloff, Mark Grimes, Ruth Kelly, Richard A. Hudson

Wayne State University

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

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Abstract

3-Trimethylaminomethyl catechol (TMC) was synthesized and shown maximally to inactivate 50% of the α-bungarotoxin (B tx) binding to the acetylcholine receptor (AcChR) from Torpedo californica electroplax. Incubation of the receptor with unsubstituted catechol produced no toxin binding inactivation of the receptor. Further, co-incubation of the receptor with 1 mM hexamethonium and 30 mM TMC effectively blocked the affinity-directed inactivation of Btx binding produced by incubation with 30 mM TMC alone. This degree of protection was consistent with the relative binding constants for hexamethonium (4.8 × 10^-6 M) and TMC (2.8 × 10^-5 M) with the AcChR. The affinity directed inactivation is suggested to be due to the covalent reaction of one or more of the quinone intermediates formed during the spontaneous oxidation of TMC with the Btx binding sites of the AcChR.

Original language	English
Pages (from-to)	1265-1272
Number of pages	8
Journal	Biochemical and Biophysical Research Communications
Volume	107
Issue number	4
DOIs	https://doi.org/10.1016/S0006-291X(82)80134-4
State	Published - Aug 31 1982

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title = "Affinity directed reactions of 3-trimethylaminomethyl catechol with the acetylcholine receptor from Torpedo californica",

abstract = "3-Trimethylaminomethyl catechol (TMC) was synthesized and shown maximally to inactivate 50% of the α-bungarotoxin (B tx) binding to the acetylcholine receptor (AcChR) from Torpedo californica electroplax. Incubation of the receptor with unsubstituted catechol produced no toxin binding inactivation of the receptor. Further, co-incubation of the receptor with 1 mM hexamethonium and 30 mM TMC effectively blocked the affinity-directed inactivation of Btx binding produced by incubation with 30 mM TMC alone. This degree of protection was consistent with the relative binding constants for hexamethonium (4.8 × 10-6 M) and TMC (2.8 × 10-5 M) with the AcChR. The affinity directed inactivation is suggested to be due to the covalent reaction of one or more of the quinone intermediates formed during the spontaneous oxidation of TMC with the Btx binding sites of the AcChR.",

author = "Nickoloff, {Brian J.} and Mark Grimes and Ruth Kelly and Hudson, {Richard A.}",

note = "Funding Information: *Supported by NIH grant NS-14491.",

year = "1982",

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doi = "10.1016/S0006-291X(82)80134-4",

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T1 - Affinity directed reactions of 3-trimethylaminomethyl catechol with the acetylcholine receptor from Torpedo californica

AU - Nickoloff, Brian J.

AU - Grimes, Mark

AU - Kelly, Ruth

AU - Hudson, Richard A.

N1 - Funding Information: *Supported by NIH grant NS-14491.

PY - 1982/8/31

Y1 - 1982/8/31

N2 - 3-Trimethylaminomethyl catechol (TMC) was synthesized and shown maximally to inactivate 50% of the α-bungarotoxin (B tx) binding to the acetylcholine receptor (AcChR) from Torpedo californica electroplax. Incubation of the receptor with unsubstituted catechol produced no toxin binding inactivation of the receptor. Further, co-incubation of the receptor with 1 mM hexamethonium and 30 mM TMC effectively blocked the affinity-directed inactivation of Btx binding produced by incubation with 30 mM TMC alone. This degree of protection was consistent with the relative binding constants for hexamethonium (4.8 × 10-6 M) and TMC (2.8 × 10-5 M) with the AcChR. The affinity directed inactivation is suggested to be due to the covalent reaction of one or more of the quinone intermediates formed during the spontaneous oxidation of TMC with the Btx binding sites of the AcChR.

AB - 3-Trimethylaminomethyl catechol (TMC) was synthesized and shown maximally to inactivate 50% of the α-bungarotoxin (B tx) binding to the acetylcholine receptor (AcChR) from Torpedo californica electroplax. Incubation of the receptor with unsubstituted catechol produced no toxin binding inactivation of the receptor. Further, co-incubation of the receptor with 1 mM hexamethonium and 30 mM TMC effectively blocked the affinity-directed inactivation of Btx binding produced by incubation with 30 mM TMC alone. This degree of protection was consistent with the relative binding constants for hexamethonium (4.8 × 10-6 M) and TMC (2.8 × 10-5 M) with the AcChR. The affinity directed inactivation is suggested to be due to the covalent reaction of one or more of the quinone intermediates formed during the spontaneous oxidation of TMC with the Btx binding sites of the AcChR.

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U2 - 10.1016/S0006-291X(82)80134-4

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SN - 0006-291X

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JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 4

ER -

Affinity directed reactions of 3-trimethylaminomethyl catechol with the acetylcholine receptor from Torpedo californica

Abstract

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