The therapeutic potential for targetting potassium channels: are dendrotoxins a suitable basis for drug design?

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Abstract

Voltage-dependent potassium ion channels have been implicated in several diseases of genetic or autoimmune origin. There are genetic defects of specific potassium channel genes in episodic ataxia with myokymia, long QT syndrome, Jervell-Lange-Nielsen syndrome, and familial hyperinsulinemic hypoglycemia of infancy. Antibodies against voltage-gated potassium channels have been detected in Isaacs syndrome (acquired neuromyotonia). Voltage-gated potassium channels have also been regarded as therapeutic targets for immuno-suppressants (targetting Kv1.3 channels) and in some neurodegenerative diseases (targetting Kv1.1 or 1.2 channels). Specific blockers of potassium channels may be designed from an understanding of the molecular recognition properties of highly specific potassium channel blocking toxins such as dendrotoxin. The dendrotoxin family of toxins and their genetic relatives in the Kunitz family of proteinase inhibitors have been studied extensively in recent years. Structural studies and functional studies with mutated toxins provide information that should help the rational design of analogues with the desired properties.

LanguageEnglish
Pages281-294
Number of pages14
JournalPerspectives in Drug Discovery and Design
Volume15
DOIs
Publication statusPublished - 31 Jan 1999

Fingerprint

Drug Design
Potassium Channels
Isaacs Syndrome
Voltage-Gated Potassium Channels
Jervell-Lange Nielsen Syndrome
Congenital Hyperinsulinism
Potassium Channel Blockers
Pharmaceutical Preparations
Neurodegenerative diseases
Long QT Syndrome
Molecular recognition
Inborn Genetic Diseases
Neurodegenerative Diseases
Autoimmune Diseases
Peptide Hydrolases
Therapeutics
Genes
Defects
Antibodies
Electric potential

Keywords

  • dendrotoxins
  • drug design
  • potassium channels
  • protein structure
  • trypsin inhibitors

Cite this

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title = "The therapeutic potential for targetting potassium channels: are dendrotoxins a suitable basis for drug design?",
abstract = "Voltage-dependent potassium ion channels have been implicated in several diseases of genetic or autoimmune origin. There are genetic defects of specific potassium channel genes in episodic ataxia with myokymia, long QT syndrome, Jervell-Lange-Nielsen syndrome, and familial hyperinsulinemic hypoglycemia of infancy. Antibodies against voltage-gated potassium channels have been detected in Isaacs syndrome (acquired neuromyotonia). Voltage-gated potassium channels have also been regarded as therapeutic targets for immuno-suppressants (targetting Kv1.3 channels) and in some neurodegenerative diseases (targetting Kv1.1 or 1.2 channels). Specific blockers of potassium channels may be designed from an understanding of the molecular recognition properties of highly specific potassium channel blocking toxins such as dendrotoxin. The dendrotoxin family of toxins and their genetic relatives in the Kunitz family of proteinase inhibitors have been studied extensively in recent years. Structural studies and functional studies with mutated toxins provide information that should help the rational design of analogues with the desired properties.",
keywords = "dendrotoxins, drug design, potassium channels, protein structure, trypsin inhibitors",
author = "Harvey, {Alan L.} and Dufton, {Mark J.}",
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T1 - The therapeutic potential for targetting potassium channels

T2 - Perspectives in Drug Discovery and Design

AU - Harvey, Alan L.

AU - Dufton, Mark J.

PY - 1999/1/31

Y1 - 1999/1/31

N2 - Voltage-dependent potassium ion channels have been implicated in several diseases of genetic or autoimmune origin. There are genetic defects of specific potassium channel genes in episodic ataxia with myokymia, long QT syndrome, Jervell-Lange-Nielsen syndrome, and familial hyperinsulinemic hypoglycemia of infancy. Antibodies against voltage-gated potassium channels have been detected in Isaacs syndrome (acquired neuromyotonia). Voltage-gated potassium channels have also been regarded as therapeutic targets for immuno-suppressants (targetting Kv1.3 channels) and in some neurodegenerative diseases (targetting Kv1.1 or 1.2 channels). Specific blockers of potassium channels may be designed from an understanding of the molecular recognition properties of highly specific potassium channel blocking toxins such as dendrotoxin. The dendrotoxin family of toxins and their genetic relatives in the Kunitz family of proteinase inhibitors have been studied extensively in recent years. Structural studies and functional studies with mutated toxins provide information that should help the rational design of analogues with the desired properties.

AB - Voltage-dependent potassium ion channels have been implicated in several diseases of genetic or autoimmune origin. There are genetic defects of specific potassium channel genes in episodic ataxia with myokymia, long QT syndrome, Jervell-Lange-Nielsen syndrome, and familial hyperinsulinemic hypoglycemia of infancy. Antibodies against voltage-gated potassium channels have been detected in Isaacs syndrome (acquired neuromyotonia). Voltage-gated potassium channels have also been regarded as therapeutic targets for immuno-suppressants (targetting Kv1.3 channels) and in some neurodegenerative diseases (targetting Kv1.1 or 1.2 channels). Specific blockers of potassium channels may be designed from an understanding of the molecular recognition properties of highly specific potassium channel blocking toxins such as dendrotoxin. The dendrotoxin family of toxins and their genetic relatives in the Kunitz family of proteinase inhibitors have been studied extensively in recent years. Structural studies and functional studies with mutated toxins provide information that should help the rational design of analogues with the desired properties.

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KW - drug design

KW - potassium channels

KW - protein structure

KW - trypsin inhibitors

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