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Autocrine‐Based Selection of Drugs That Target Ion Channels from Combinatorial Venom Peptide Libraries |
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| Authors: | Dr. Hongkai Zhang Dr. Mingjuan Du Dr. Jia Xie Xiao Liu Jingying Sun Dr. Wei Wang Xiu Xin Prof. Lourival D. Possani Dr. Kyungmoo Yea Prof. Richard A. Lerner |
| Affiliation: | 1. Department of Molecular and Cellular Biology, The Scripps Research Institute, La Jolla, CA, USA;2. The institute for Advanced Immunochemical Studies, Shanghai Tech University, Shanghai, P.R.China;3. Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México |
| Abstract: | Animal venoms represent a rich source of pharmacologically active peptides that interact with ion channels. However, a challenge to discovering drugs remains because of the slow pace at which venom peptides are discovered and refined. An efficient autocrine‐based high‐throughput selection system was developed to discover and refine venom peptides that target ion channels. The utility of this system was demonstrated by the discovery of novel Kv1.3 channel blockers from a natural venom peptide library that was formatted for autocrine‐based selection. We also engineered a Kv1.3 blocker peptide (ShK) derived from sea anemone to generate a subtype‐selective Kv1.3 blocker with a long half‐life in vivo. |
| Keywords: | drug discovery ion channels peptide drugs peptides venom peptides |