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International Journal Of Bilogical Sciences

.: Home > International Journal Of Bilogical Sciences > 2014 > Volume 10 Number 10 > Qiang Du1, 2,, Xiaojuan Hou1, 2,, Lilin Ge2,, Renjie Li2, Mei Zhou2, Hui Wang1, 2, , Lei Wang2, , Minjie Wei1, Tianbao Chen2 and Chris Shaw

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

Qiang Du1, 2,, Xiaojuan Hou1, 2,, Lilin Ge2,, Renjie Li2, Mei Zhou2, Hui Wang1, 2, , Lei Wang2, , Minjie Wei1, Tianbao Chen2 and Chris Shaw
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 These authors contributed equally to this work.  Corresponding authors: 1073075810@qq.com or l.wang@qub.ac.uk.
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.

Keywords :
Scorpion; Venom; Molecular Cloning; Antimicrobial; Peptide; analogue design.

Date Deposited : 15 Feb 2016 10:32

Last Modified : 15 Feb 2016 10:32

Official URL: http://www.ijbs.com/v10i10

Volume 10, Number 10, - 2014 , ISSN 1449-2288

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