title: AaeAP1 and AaeAP2: novel antimicrobial peptides from the venom of the scorpion, Androctonus aeneas: structural characterisation, molecular cloning of biosynthetic precursor-encoding cDNAs and engineering of analogues with enhanced antimicrobial and anticancer activities.
abstract: The main functions of the abundant polypeptide toxins present in scorpion venoms are the debilitation of arthropod prey or defence against predators. These effects are achieved mainly through the blocking of an array of ion channel types within the membranes of excitable cells. However, while these ion channel-blocking toxins are tightly-folded by multiple disulphide bridges between cysteine residues, there are additional groups of peptides in the venoms that are devoid of cysteine residues. These non-disulphide bridged peptides are the subject of much research interest, and among these are peptides that exhibit antimicrobial activity. Here, we describe two novel non-disulphide-bridged antimicrobial peptides that are present in the venom of the North African scorpion, Androctonus aeneas. The cDNAs encoding the biosynthetic precursors of both peptides were cloned from a venom-derived cDNA library using 3'- and 5'-RACE strategies. Both translated precursors contained open-reading frames of 74 amino acid residues, each encoding one copy of a putative novel nonadecapeptide, whose primary structures were FLFSLIPSVIAGLVSAIRN and FLFSLIPSAIAGLVSAIRN, respectively. Both peptides were C-terminally amidated. Synthetic versions of each natural peptide displayed broad-spectrum antimicrobial activities, but were devoid of antiproliferative activity against human cancer cell lines. However, synthetic analogues of each peptide, engineered for enhanced cationicity and amphipathicity, exhibited increases in antimicrobial potency and acquired antiproliferative activity against a range of human cancer cell lines. These data clearly illustrate the potential that natural peptide templates provide towards the design of synthetic analogues for therapeutic exploitation.
authors.affiliation: School of Pharmaceutical Sciences, China Medical University, Shenyang 110001, China. qdu01@qub.ac.uk.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Du
authors.affiliation: School of Pharmaceutical Sciences, China Medical University, Shenyang 110001, China. xhou01@qub.ac.uk.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Hou
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. l.wang@qub.ac.uk.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. zhangyingqi08@sina.com.
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. xxi01@qub.ac.uk.
authors.forename: Xinping
authors.initials: X
authors.lastname: Xi
authors.affiliation: School of Pharmaceutical Sciences, China Medical University, Shenyang 110001, China. wanghuiheidi@126.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. m.zhou@qub.ac.uk.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. dja@njutcm.edu.cn.
authors.forename: Jinao
authors.initials: J
authors.lastname: Duan
authors.affiliation: School of Pharmaceutical Sciences, China Medical University, Shenyang 110001, China. mjwei@hotmail.com.
authors.forename: Minjie
authors.initials: M
authors.lastname: Wei
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. t.chen@qub.ac.uk.
authors.forename: Tianbao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK. chris.shaw@qub.ac.uk.
authors.forename: Chris
authors.initials: C
authors.lastname: Shaw
mesh_terms: D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001483:Base Sequence; D002176:Candida albicans / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018076:DNA, Complementary / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D015723:Gene Library; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D015202:Protein Engineering; D012604:Scorpion Venoms / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D018076:DNA, Complementary; D012604:Scorpion Venoms