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In silico screening, analysis, and modelling for a novel anticancer peptide

Cancer is currently one of the leading causes of mortality and morbidity worldwide. Most anticancer therapies rely on small molecule drugs (<0.5 kDa). As with all small molecule drugs, chemotherapy is highly toxic and presents many off-target side effects. Peptide drugs offer improved specificity an...

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Main Author: Abdou, Youssef
Format: Thesis
Published: AUC Knowledge Fountain 2016
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access_status_str Open Access
author Abdou, Youssef
author_browse Abdou, Youssef
author_facet Abdou, Youssef
author_sort Abdou, Youssef
collection Thesis
dc_rights_str_mv The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy.
description Cancer is currently one of the leading causes of mortality and morbidity worldwide. Most anticancer therapies rely on small molecule drugs (<0.5 kDa). As with all small molecule drugs, chemotherapy is highly toxic and presents many off-target side effects. Peptide drugs offer improved specificity and are cheaper and more accessible to manufacture. In this study, we have developed a support vector machine (SVM) model in order to detect peptide sequences with potential anticancer activity through scanning the Red Sea Metagenomic library. Furthermore, we conducted an in silico study in order to analyze one of the peptides returned by the SVM pipeline and assessed its cytotoxicity and the mode of cell death by conducting MTT and Annexin V staining assays, respectively. We observed that the selected anticancer peptide contains the C-terminal portion of the homeodomain structure, of human Pax6, an antennapedia homeodomain region, and can bind DNA. Furthermore, we observed dose-response cytotoxicity of HepG2 cells with our peptide. No such cytotoxicity was observed in HeLa cells; a morphological change, however, was observed. We examined the cytotoxicity of our drug against 1BR-hTERT normal skin cells. Our peptide drug induced dose-dependent cytotoxicity that was markedly weaker than that of cancer treated cells. Together our data illustrates the isolation of one peptide drug candidate from the AUC Red Sea metagenomic library; furthermore, we were able to observe the selective dose-dependent reduction of HepG2 cell viability
format Thesis
id oai:fount.aucegypt.edu:etds-1359
institution American University in Cairo (Egypt)
last_indexed 2026-06-10T12:35:41.195Z
license_str Other — see source repository
provenance_str_mv Harvested via OAI-PMH from AUC Knowledge Fountain — bepress
publishDate 2016
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spelling oai:fount.aucegypt.edu:etds-1359 In silico screening, analysis, and modelling for a novel anticancer peptide Abdou, Youssef Cancer is currently one of the leading causes of mortality and morbidity worldwide. Most anticancer therapies rely on small molecule drugs (<0.5 kDa). As with all small molecule drugs, chemotherapy is highly toxic and presents many off-target side effects. Peptide drugs offer improved specificity and are cheaper and more accessible to manufacture. In this study, we have developed a support vector machine (SVM) model in order to detect peptide sequences with potential anticancer activity through scanning the Red Sea Metagenomic library. Furthermore, we conducted an in silico study in order to analyze one of the peptides returned by the SVM pipeline and assessed its cytotoxicity and the mode of cell death by conducting MTT and Annexin V staining assays, respectively. We observed that the selected anticancer peptide contains the C-terminal portion of the homeodomain structure, of human Pax6, an antennapedia homeodomain region, and can bind DNA. Furthermore, we observed dose-response cytotoxicity of HepG2 cells with our peptide. No such cytotoxicity was observed in HeLa cells; a morphological change, however, was observed. We examined the cytotoxicity of our drug against 1BR-hTERT normal skin cells. Our peptide drug induced dose-dependent cytotoxicity that was markedly weaker than that of cancer treated cells. Together our data illustrates the isolation of one peptide drug candidate from the AUC Red Sea metagenomic library; furthermore, we were able to observe the selective dose-dependent reduction of HepG2 cell viability 2016-02-01T08:00:00Z thesis application/pdf https://fount.aucegypt.edu/etds/360 https://fount.aucegypt.edu/context/etds/article/1359/viewcontent/Youssef_20abdou_20Thesis_20Final_20Bound_20Modifications.pdf The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy. Theses and Dissertations AUC Knowledge Fountain anticancer peptides anticancer
spellingShingle anticancer peptides
anticancer
Abdou, Youssef
In silico screening, analysis, and modelling for a novel anticancer peptide
title In silico screening, analysis, and modelling for a novel anticancer peptide
title_full In silico screening, analysis, and modelling for a novel anticancer peptide
title_fullStr In silico screening, analysis, and modelling for a novel anticancer peptide
title_full_unstemmed In silico screening, analysis, and modelling for a novel anticancer peptide
title_short In silico screening, analysis, and modelling for a novel anticancer peptide
title_sort in silico screening analysis and modelling for a novel anticancer peptide
topic anticancer peptides
anticancer
url https://fount.aucegypt.edu/etds/360
https://fount.aucegypt.edu/context/etds/article/1359/viewcontent/Youssef_20abdou_20Thesis_20Final_20Bound_20Modifications.pdf
work_keys_str_mv AT abdouyoussef insilicoscreeninganalysisandmodellingforanovelanticancerpeptide