Designing of peptides with desired half-life in intestine-like environment

Handle URI:
http://hdl.handle.net/10754/334565
Title:
Designing of peptides with desired half-life in intestine-like environment
Authors:
Sharma, Arun; Singla, Deepak; Rashid, Mamoon ( 0000-0003-4851-4994 ) ; Raghava, Gajendra Pal Singh
Abstract:
Background: In past, a number of peptides have been reported to possess highly diverse properties ranging from cell penetrating, tumor homing, anticancer, anti-hypertensive, antiviral to antimicrobials. Owing to their excellent specificity, low-toxicity, rich chemical diversity and availability from natural sources, FDA has successfully approved a number of peptide-based drugs and several are in various stages of drug development. Though peptides are proven good drug candidates, their usage is still hindered mainly because of their high susceptibility towards proteases degradation. We have developed an in silico method to predict the half-life of peptides in intestine-like environment and to design better peptides having optimized physicochemical properties and half-life.Results: In this study, we have used 10mer (HL10) and 16mer (HL16) peptides dataset to develop prediction models for peptide half-life in intestine-like environment. First, SVM based models were developed on HL10 dataset which achieved maximum correlation R/R2 of 0.57/0.32, 0.68/0.46, and 0.69/0.47 using amino acid, dipeptide and tripeptide composition, respectively. Secondly, models developed on HL16 dataset showed maximum R/R2 of 0.91/0.82, 0.90/0.39, and 0.90/0.31 using amino acid, dipeptide and tripeptide composition, respectively. Furthermore, models that were developed on selected features, achieved a correlation (R) of 0.70 and 0.98 on HL10 and HL16 dataset, respectively. Preliminary analysis suggests the role of charged residue and amino acid size in peptide half-life/stability. Based on above models, we have developed a web server named HLP (Half Life Prediction), for predicting and designing peptides with desired half-life. The web server provides three facilities; i) half-life prediction, ii) physicochemical properties calculation and iii) designing mutant peptides.Conclusion: In summary, this study describes a web server 'HLP' that has been developed for assisting scientific community for predicting intestinal half-life of peptides and to design mutant peptides with better half-life and physicochemical properties. HLP models were trained using a dataset of peptides whose half-lives have been determined experimentally in crude intestinal proteases preparation. Thus, HLP server will help in designing peptides possessing the potential to be administered via oral route (http://www.imtech.res.in/raghava/hlp/).
KAUST Department:
Marine Science Program
Citation:
Sharma A, Singla D, Rashid M, Raghava GP (2014) Designing of peptides with desired half-life in intestine-like environment. BMC Bioinformatics 15: 282. doi:10.1186/1471-2105-15-282.
Publisher:
BioMed Central
Journal:
BMC Bioinformatics
Issue Date:
20-Aug-2014
DOI:
10.1186/1471-2105-15-282
PubMed ID:
25141912
PubMed Central ID:
PMC4150950
Type:
Article
ISSN:
14712105
Appears in Collections:
Articles; Marine Science Program

Full metadata record

DC FieldValue Language
dc.contributor.authorSharma, Arunen
dc.contributor.authorSingla, Deepaken
dc.contributor.authorRashid, Mamoonen
dc.contributor.authorRaghava, Gajendra Pal Singhen
dc.date.accessioned2014-11-11T14:29:50Z-
dc.date.available2014-11-11T14:29:50Z-
dc.date.issued2014-08-20en
dc.identifier.citationSharma A, Singla D, Rashid M, Raghava GP (2014) Designing of peptides with desired half-life in intestine-like environment. BMC Bioinformatics 15: 282. doi:10.1186/1471-2105-15-282.en
dc.identifier.issn14712105en
dc.identifier.pmid25141912en
dc.identifier.doi10.1186/1471-2105-15-282en
dc.identifier.urihttp://hdl.handle.net/10754/334565en
dc.description.abstractBackground: In past, a number of peptides have been reported to possess highly diverse properties ranging from cell penetrating, tumor homing, anticancer, anti-hypertensive, antiviral to antimicrobials. Owing to their excellent specificity, low-toxicity, rich chemical diversity and availability from natural sources, FDA has successfully approved a number of peptide-based drugs and several are in various stages of drug development. Though peptides are proven good drug candidates, their usage is still hindered mainly because of their high susceptibility towards proteases degradation. We have developed an in silico method to predict the half-life of peptides in intestine-like environment and to design better peptides having optimized physicochemical properties and half-life.Results: In this study, we have used 10mer (HL10) and 16mer (HL16) peptides dataset to develop prediction models for peptide half-life in intestine-like environment. First, SVM based models were developed on HL10 dataset which achieved maximum correlation R/R2 of 0.57/0.32, 0.68/0.46, and 0.69/0.47 using amino acid, dipeptide and tripeptide composition, respectively. Secondly, models developed on HL16 dataset showed maximum R/R2 of 0.91/0.82, 0.90/0.39, and 0.90/0.31 using amino acid, dipeptide and tripeptide composition, respectively. Furthermore, models that were developed on selected features, achieved a correlation (R) of 0.70 and 0.98 on HL10 and HL16 dataset, respectively. Preliminary analysis suggests the role of charged residue and amino acid size in peptide half-life/stability. Based on above models, we have developed a web server named HLP (Half Life Prediction), for predicting and designing peptides with desired half-life. The web server provides three facilities; i) half-life prediction, ii) physicochemical properties calculation and iii) designing mutant peptides.Conclusion: In summary, this study describes a web server 'HLP' that has been developed for assisting scientific community for predicting intestinal half-life of peptides and to design mutant peptides with better half-life and physicochemical properties. HLP models were trained using a dataset of peptides whose half-lives have been determined experimentally in crude intestinal proteases preparation. Thus, HLP server will help in designing peptides possessing the potential to be administered via oral route (http://www.imtech.res.in/raghava/hlp/).en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.rightsThis article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleDesigning of peptides with desired half-life in intestine-like environmenten
dc.typeArticleen
dc.contributor.departmentMarine Science Programen
dc.identifier.journalBMC Bioinformaticsen
dc.identifier.pmcidPMC4150950en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorRashid, Mamoonen

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