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- Title
Structure-Activity Relationship of a Highly Selective Peptidyl Inhibitor of Kv1.3 Voltage-Gated K-Channel from Scorpion ( B. sindicus) Venom.
- Authors
Ali, Syed; Alam, Mehtab; Abbasi, Atiya; Kalbacher, Hubert; Schaechinger, Thorsten; Hu, Youtian; Zhijian, Cao; Li, Wenxin; Voelter, Wolfgang
- Abstract
Venomous fauna of the world is a unique source of protein and peptide toxins with a wide range of pharmacological and physiological activities targeting in particular the bio-signaling system. Thus the most widely known source of peptidyl neurotoxins used for callipering different ion channels (e.g. Na, K, Ca or Cl etc.) as well as many medicinally important peptides which have been accepted as drugs or are in clinical trials originate from the venom of scorpions of Buthidae family. In the present study, structure-activity relationship of highly selective short-chain neurotoxin from scorpion Buthus sindicus (a common yellow scorpion of Sindh, Pakistan) has been established. The toxin named as Bs-KTx6 (4,115.4 Da) has been isolated, synthesized and found to be a potent as well as selective inhibitor of voltage gated potassium channel Kv1.3 (IC = 7.7 pM). The structural studies on channel selective modulators like Bs-KTx6 may serve as a possible template in establishing libraries of peptidyl toxins for treating diseases such as multiple sclerosis, type-1 diabetes mellitus, rheumatoid arthritis, allergic contact dermatitis, bone resorption due to periodontitis and delayed type hypersensitivity. It is also worth mentioning that the peptide based drugs have excellent safety profiles as well as selectivity compared to other non-protein molecules. In conclusion, identified peptide Bs-KTx6 is a specific as well as very selective blocker of Kv1.3 and provides a starting template for the synthesis of peptidyl drugs to treat autoimmune diseases.
- Subjects
STRUCTURE-activity relationships; ENZYME inhibitors; POTASSIUM channels; SCORPION venom; AUTOIMMUNE disease treatment
- Publication
International Journal of Peptide Research & Therapeutics, 2014, Vol 20, Issue 1, p19
- ISSN
1573-3149
- Publication type
Article
- DOI
10.1007/s10989-013-9362-z