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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.

SUBMITTER: Du Q

PROVIDER: S-EPMC4202026 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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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.

Du Qiang Q Hou Xiaojuan X Ge Lilin L Li Renjie R Zhou Mei M Wang Hui H Wang Lei L Wei Minjie M Chen Tianbao T Shaw Chris C

International journal of biological sciences 20140921 10

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 isol ...[more]

PMID: 25332684

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Project description:In the present study, we report for the first time a proteomic profile of Buthotus saulcyi, Odontobuthus doriae and Androctonus crassicauda scorpion venom with the aim of looking ahead and determining the structural and functional characteristics of these compounds for use as medical tools. Molecular weight determination of isolated proteins was performed in order to better describe the B. saulcyi, O. doriae and A. crassicauda raw toxin proteins by both polyacrylamide electrophoresis and two-dimensional electrophoresis. 2D-PAGE data from the B. saulcyi, O. doriae and A. crassicauda raw toxin showed a molecular weight between 3.6 and 205 kDa (for B. saulcyi), 6.6 to 205 kDa (for O. doriae) and 6.6-109 kDa (for A. crassicauda). Then 14, 14 and 21 fractions of crude toxins were isolated using HPLC and their protein content was estimated for B. saulcyi, O. doriae and A. crassicauda, respectively. SDS-PAGE analysis of selected fractions of crude toxin showed 9 protein bands with a molecular weight between 13 and 217 kDa for B. saulcyi, 10 protein bands with a molecular weight between 3.8 to182 kDa for O. doriae and 5 protein bands with a molecular weight between 5.99 and 41.65 kDa for A. crassicauda. In case of B. saulcyi, the fraction 7 (F7) showed more cytotoxicity than other isolated fractions. Subsequently, the amino acid sequencing of fraction 7 led us to two protein bands designated as p3 and p4 peptide. For O. doriae, the peptide fraction of F17, obtained from the crude venoms of O. doriae scorpion, was found to be more cytotoxic than the crude venoms and other isolated fractions. Furthermore, F5 demonstrated significant anti-proliferative and apoptotic activity. Therefore, we performed PAGE on fraction F5 and found 5 protein bands. The two protein bands, each from fraction F5 that marked as P1 and P2 were selected for amino acid sequencing. The three peptide fractions F17, obtained from the crude venoms of A. crassicauda scorpion, was found to be more cytotoxic than the crude venoms and other isolated fractions. Furthermore, F17 demonstrated significant anti-proliferative and apoptotic activity. This makes this fraction better candidate for searching the peptide that might be used for selective killing of cancerous cells. Therefore, we performed PAGE on fractionsF17, and found 2 protein bands. One protein band from fraction F17 that marked as P5 was selected for amino acid sequencing. Finally, these protein bands were removed and molecular mass and amino acid sequence analysis was performed using Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS). In-silico studies of P1, P2, P3, P4 and P5 for protein sequence alignment showed the most similarity with Hemoglobin beta-2 chain protein, Chaperonin HSP60, Chrysophsin2, pheromone-bound protein 2 and Trypsin- like serine proteinase, respectively

Project description:Background and aimScorpion envenomation is a common acute life threatening health problem in developing countries as Egypt. Scorpion venom is a complex structure composed of neurotoxic proteins, salts, acidic proteins, and organic compounds, thereby having of neurologic, cardiovascular, hematologic, and renal side effects, in addition to local effects such as redness, pain, burning, and swelling.AimsThe study consisted of two parts to describe demographic characteristics, toxicological manifestations of scorpion sting cases in Luxor, Egypt and morphological characterization of the commonest scorpion species in the studied community for easy rapid identification of scorpion species by doctors from the patient history to provide better choices of management.Materials & methodsFirst part of the study include all cases of scorpion envenomation attending General Hospital of Esna, Luxor, Egypt during the period of scorpion activity 2017, demographic data was collected then cases were assessed for clinical manifestations, ECG, complications and deaths related to scorpion species. Second part: scorpions were collected from areas around patient housing for morphological description of their sense organs and venom apparatus by Scanning Electron Microscopy.ResultsA total of 110 cases of scorpion stings were reviewed, males 81 (72.9%) and females 30 (27.1%), with a mean age of 31.9 ± 17.9 years. Localized pain was the most frequent presenting complaint (89 80.2%), vomiting was the commonest clinical symptom (90.9%). All scorpion stings were due to the most endemic species in North Africa, Leiurusquinquestriatus & Androctonuscrassicauda. Death rate among cases was (5.5%) all were Abroug's Grade III. Cardiac dysrhythmia and subsequent pulmonary edema were the commonest cause of death. Clinical manifestations were more sever in Leiurus quinquestriatus stings while death rate was more in Androctonus crassicauda stings. The morphological characterization of the sense organs (eyes, pedipalps, pectines& sensory setae) and venom apparatus of the scorpions L. quinquestriatus & A. crassicauda were described by Scanning Electron Microscopy.ConclusionScorpion sting is an acute heath threating in Southern Egypt, Leiurus quinquestriatus & Androctonus crassicauda are most endemic scorpion species in Southern Egypt. More attention for scorpion envenomation in such subtropical hyper desert localities is required to eradicate toxic scorpion species and prevent possible causes of deaths.

Dataset Information

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.

Publications

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.

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