Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
XB-ART-39924
ChemMedChem 2009 Mar 01;43:406-14. doi: 10.1002/cmdc.200800292.
Show Gene links Show Anatomy links

Structurally minimized mu-conotoxin analogues as sodium channel blockers: implications for designing conopeptide-based therapeutics.

Han TS , Zhang MM , Walewska A , Gruszczynski P , Robertson CR , Cheatham TE , Yoshikami D , Olivera BM , Bulaj G .


???displayArticle.abstract???
Disulfide bridges that stabilize the native conformation of conotoxins pose a challenge in the synthesis of smaller conotoxin analogues. Herein we describe the synthesis of a minimized analogue of the analgesic mu-conotoxin KIIIA that blocks two sodium channel subtypes, the neuronal Na(V)1.2 and skeletal muscle Na(V)1.4. Three disulfide-deficient analogues of KIIIA were initially synthesized in which the native disulfide bridge formed between either C1-C9, C2-C15, or C4-C16 was removed. Deletion of the first bridge only slightly affected the peptide's bioactivity. To further minimize this analogue, the N-terminal residue was removed and two nonessential serine residues were replaced by a single 5-amino-3-oxapentanoic acid residue. The resulting "polytide" analogue retained the ability to block sodium channels and to produce analgesia. Until now, the peptidomimetic approach applied to conotoxins has progressed only modestly at best; thus, the disulfide-deficient analogues containing backbone spacers provide an alternative advance toward the development of conopeptide-based therapeutics.

???displayArticle.pubmedLink??? 19107760
???displayArticle.pmcLink??? PMC4074532
???displayArticle.link??? ChemMedChem
???displayArticle.grants??? [+]


References [+] :
Amir, The role of sodium channels in chronic inflammatory and neuropathic pain. 2006, Pubmed