title: Purification, characterization, and bioactivity of a new analgesic-antitumor peptide from Chinese scorpion Buthus martensii Karsch.
abstract: Scorpion venoms are complex mixtures of dozens or even hundreds of distinct proteins, many of which have diverse bioactivities. In this study, after bioassay-driven chromatographic purification, a new dual-function peptide with analgesic and antitumor activities was isolated and designated BmK AGAP-SYPU2. The first 12 amino acid residues were sequenced with Edman degradation. The cDNA was cloned by using rapid amplification of cDNA ends from the cDNA pool from scorpion glands. The amino acid sequence of BmK AGAP-SYPU2 was then deduced, and is consistent with the molecular mass measured with MALDI-TOF-MS. A preliminary pharmacological analysis revealed the following: in the dose-effect curve plotted with the mouse-twisting test, BmK AGAP-SYPU2 showed analgesic activity with an ED50 value of 1.42 mg/kg; in the time-effect curves plotted with a hot-plate procedure, BmK AGAP-SYPU2 had similar effects to those of the painkiller morphine, except for its longer duration. BmK AGAP-SYPU2 also showed antitumor activity against Ehrlich ascites tumor and S-180 fibrosarcoma models in vivo. Sequence alignment and homology modeling showed that BmK AGAP-SYPU2 is highly conserved relative to other scorpion α-toxins. However, a few different amino acids endow it with unique molecular properties, which may be responsible for its specific bioactivities. BmK AGAP-SYPU2, a new scorpion neurotoxin with dual functions, is a potential candidate drug amenable to exploitation and modification.
authors.affiliation: School of Life Science and Bio-pharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning Province 110016, PR China; Yangzhou University, College of Bioscience and Biotechnology, Yangzhou, Jiangsu Province 225009, PR China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Shao
authors.affiliation: School of Life Science and Bio-pharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning Province 110016, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Benxi Institute of Pharmaceutical Research, Shenyang Pharmaceutical University, Benxi, Liaoning Province 117004, PR China.
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Zhao
authors.affiliation: Benxi Institute of Pharmaceutical Research, Shenyang Pharmaceutical University, Benxi, Liaoning Province 117004, PR China.
authors.forename: Chun-Fu
authors.initials: CF
authors.lastname: Wu
authors.affiliation: Benxi Institute of Pharmaceutical Research, Shenyang Pharmaceutical University, Benxi, Liaoning Province 117004, PR China. Electronic address: liuyanfeng@hotmail.com.
authors.forename: Yan-Feng
authors.initials: YF
authors.lastname: Liu
authors.affiliation: School of Life Science and Bio-pharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning Province 110016, PR China. Electronic address: Jinghaizhang82@gmail.com.
authors.forename: Jing-Hai
authors.initials: JH
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000700:Analgesics / Q000737:chemistry / Q000302:isolation & purification* / Q000627:therapeutic use*; D000818:Animals; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy; D012604:Scorpion Venoms / Q000737:chemistry / Q000302:isolation & purification* / Q000627:therapeutic use*
chemical_list: D000700:Analgesics; D012604:Scorpion Venoms; C477804:antitumor-analgesic peptide, Buthus martensii
keywords: Analgesic activity; Antitumor activity; BmK AGAP-SYPU2; Buthus martensii Karsch; Purification; cDNA clone