2ak0
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(New page: 200px<br /><applet load="2ak0" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ak0" /> '''Structure of cyclic conotoxin MII-7'''<br />...)
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Revision as of 06:03, 21 November 2007
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Structure of cyclic conotoxin MII-7
Overview
Conotoxins (CTXs), with their exquisite specificity and potency, have, recently created much excitement as drug leads. However, like most, peptides, their beneficial activities may potentially be undermined by, susceptibility to proteolysis in vivo. By cyclizing the alpha-CTX MII by, using a range of linkers, we have engineered peptides that preserve their, full activity but have greatly improved resistance to proteolytic, degradation. The cyclic MII analogue containing a seven-residue linker, joining the N and C termini was as active and selective as the native, peptide for native and recombinant neuronal nicotinic acetylcholine, receptor subtypes present in bovine chromaffin cells and expressed in, Xenopus oocytes, respectively. Furthermore, its resistance to proteolysis, against a specific protease and in human plasma was significantly, improved. More generally, to our knowledge, this report is the first on, the cyclization of disulfide-rich toxins. Cyclization strategies represent, an approach for stabilizing bioactive peptides while keeping their full, potencies and should boost applications of peptide-based drugs in human, medicine.
About this Structure
2AK0 is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
Engineering stable peptide toxins by means of backbone cyclization: stabilization of the alpha-conotoxin MII., Clark RJ, Fischer H, Dempster L, Daly NL, Rosengren KJ, Nevin ST, Meunier FA, Adams DJ, Craik DJ, Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13767-72. Epub 2005 Sep 14. PMID:16162671
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