title: Autocrine-Based Selection of Drugs That Target Ion Channels from Combinatorial Venom Peptide Libraries.
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.
authors.affiliation: Department of Molecular and Cellular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA. hongkai@scripps.edu.
authors.forename: Hongkai
authors.initials: H
authors.lastname: Zhang
authors.affiliation: The institute for Advanced Immunochemical Studies, Shanghai Tech University, 99 Haike Road, Pudong, Shanghai, 201210, P.R.China.
authors.forename: Mingjuan
authors.initials: M
authors.lastname: Du
authors.affiliation: Department of Molecular and Cellular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Xie
authors.affiliation: The institute for Advanced Immunochemical Studies, Shanghai Tech University, 99 Haike Road, Pudong, Shanghai, 201210, P.R.China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: The institute for Advanced Immunochemical Studies, Shanghai Tech University, 99 Haike Road, Pudong, Shanghai, 201210, P.R.China.
authors.forename: Jingying
authors.initials: J
authors.lastname: Sun
authors.affiliation: The institute for Advanced Immunochemical Studies, Shanghai Tech University, 99 Haike Road, Pudong, Shanghai, 201210, P.R.China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: The institute for Advanced Immunochemical Studies, Shanghai Tech University, 99 Haike Road, Pudong, Shanghai, 201210, P.R.China.
authors.forename: Xiu
authors.initials: X
authors.lastname: Xin
authors.affiliation: Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Apartado Postal 510-3, Cuernavaca, Morelos, 62250, México.
authors.forename: Lourival D
authors.initials: LD
authors.lastname: Possani
authors.affiliation: Department of Molecular and Cellular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
authors.forename: Kyungmoo
authors.initials: K
authors.lastname: Yea
authors.affiliation: Department of Molecular and Cellular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA. rlerner@scripps.edu.
authors.forename: Richard A
authors.identifier: 0000-0003-4399-874X
authors.initials: RA
authors.lastname: Lerner
mesh_terms: D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D057166:High-Throughput Screening Assays; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors*; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D014688:Venoms / Q000737:chemistry*
chemical_list: D001688:Biological Products; D051664:Kv1.3 Potassium Channel; D019151:Peptide Library; D010455:Peptides; D026902:Potassium Channel Blockers; D014688:Venoms
keywords: drug discovery; ion channels; peptide drugs; peptides; venom peptides