Ion channel toxins as molecular models for the design of new drugs = Toksini, ki delujejo na ionske kanalčke, kot molekularni modeli za načrtovanjenovih zdravil
Kem, William R
Naturally occurring toxins possessing high affinity and selectivity for particular cell receptors, besides being excellent molecular probes in biomedical research, can also serve as lead compounds ...for drug design. Manipulation of their structures can often reduce their toxicity without abolishing therapeutically useful effects. Such toxins have already been discovered in most cases. Two examples of this drug development approach will be presented: (1) a nemertine worm toxin (the bicyclic alkaloid anabascine), when derivatized with an aromatic aldehyde, yielded a compound which selectively stimulates brain alpha7 nicotinic receptors and enhances cognition. DMXBA (GTS- 21) also displays neuroprotective activily and is much less toxic than nicotine. While some nicotinic receptors disappear as Alzheimer's disease progresses, alpha7 rcceptors are not greatly affected and therefore can continue to serve as a CNS drug target. It was recently demonstrated that the primary metabolites of DMXBA are even more potent alpha7agonists than the parent compound. (2) A new K channel peptide toxin, ShK, found in the sea anemone Stichodacryla helianthus has been synthesized bysolid-phase melhods. The NMR-derived solution structure of this 35 residue peptide contains a scaffold consisting of two short alpha-helices separated bya beta turn, in contrast to the beta-sheet scaffold present in the scorpion toxin charbydoloxin which interacts with the same external site in certain voltage- and Ca-gated K channels. The homomeric Kv1.3 channel is largely confined lo the T-lymphocyte cell surface. Toxin blockade of this channel inhibits proliferation of these cells in vitro and the development of a delayed type hypersensitivity reaction in vivo. (Abstract truncated at 2000 characters).
It was not necessary to add the material to the shelf.
Bibliographic material was successfully added on shelf.
Adding bibliographical material on shelf was not successful.
Material is already on the shelf.
Permalink
URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year
Impact factor
Edition
Category
Classification
JCR
SNIP
JCR
SNIP
JCR
SNIP
JCR
SNIP
Select the library membership card:
DRS,
in which the journal is indexed
Database name
Field
Year
Links to authors' personal bibliographies
Links to information on researchers in the SICRIS system
Subject headings in COBISS General List of Subject Headings
Select pickup location
The material from the parent unit is free. If the material is delivered to the pickup location from another unit, the library may charge you for this service.
