title: Cationicity-enhanced analogues of the antimicrobial peptides, AcrAP1 and AcrAP2, from the venom of the scorpion, Androctonus crassicauda, display potent growth modulation effects on human cancer cell lines.
abstract: The non disulphide-bridged peptides (NDBPs) of scorpion venoms are attracting increased interest due to their structural heterogeneity and broad spectrum of biological activities. Here, two novel peptides, named AcrAP1 and AcrAP2, have been identified in the lyophilised venom of the Arabian scorpion, Androctonus crassicauda, through "shotgun" molecular cloning of their biosynthetic precursor-encoding cDNAs. The respective mature peptides, predicted from these cloned cDNAs, were subsequently isolated from the same venom sample using reverse phase HPLC and their identities were confirmed by use of mass spectrometric techniques. Both were found to belong to a family of highly-conserved scorpion venom antimicrobial peptides - a finding confirmed through the biological investigation of synthetic replicates. Analogues of both peptides designed for enhanced cationicity, displayed enhanced potency and spectra of antimicrobial activity but, unlike the native peptides, these also displayed potent growth modulation effects on a range of human cancer cell lines. Thus natural peptide templates from venom peptidomes can provide the basis for rational analogue design to improve both biological potency and spectrum of action. The diversity of such templates from such natural sources undoubtedly provides the pharmaceutical industry with unique lead compounds for drug discovery.
authors.affiliation: 1. School of Pharmaceutical Sciences, China Medical University, Shenyang 110001, Liaoning, PR China ; 2. Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Du
authors.affiliation: 1. School of Pharmaceutical Sciences, China Medical University, Shenyang 110001, Liaoning, PR China ; 2. Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Hou
authors.affiliation: 2. Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: Lilin
authors.initials: L
authors.lastname: Ge
authors.affiliation: 2. Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: Renjie
authors.initials: R
authors.lastname: Li
authors.affiliation: 2. Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhou
authors.affiliation: 1. School of Pharmaceutical Sciences, China Medical University, Shenyang 110001, Liaoning, PR China ; 2. Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: 2. Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: 1. School of Pharmaceutical Sciences, China Medical University, Shenyang 110001, Liaoning, PR China.
authors.forename: Minjie
authors.initials: M
authors.lastname: Wei
authors.affiliation: 2. Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: Tianbao
authors.initials: T
authors.lastname: Chen
authors.affiliation: 2. Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Shaw
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D055808:Drug Discovery / Q000379:methods*; D006461:Hemolysis; D006736:Horses; D006801:Humans; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D012604:Scorpion Venoms / Q000737:chemistry*; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D023181:Antimicrobial Cationic Peptides; D017931:DNA Primers; D018076:DNA, Complementary; D012604:Scorpion Venoms; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue
keywords: Antimicrobial; Molecular Cloning; Peptide; Scorpion; Venom; analogue design.