Determination of half-life of novel peptides in blood is one of the major challenges in understanding their stability. These methods not only enhance the in-vivo half-life but also increase bioavailability. In the past, numerous attempts have been made to increase the half-life of peptides in blood that includes cyclization of peptides, incorporation of modified residues and terminal modifications. The parenteral route of peptide delivery is preferred over other routes of administration for efficient systemic delivery as it prevents cleavage of peptides by the gastrointestinal enzymes. Different routes of peptide deliveries have been explored that include intranasal, transdermal, oral, pulmonary, rectal. The major hurdle that is blocking the path of development of therapeutic peptides is their short half-life due to their susceptibility to enzymatic degradation that reduces their bioavailability. Despite many advantages, therapeutic peptides still face many roadblocks on the road to the pharmaceutical market. The peptides have a number of advantages over small molecule-based drugs that include high specificity and low side effects. Peptides show diverse therapeutic properties like anticancer, antimicrobial, antiparasitic, cell penetrating, antihypertensive, tumor homing. The technological advances have led to the revival of interest of the pharmaceutical industry in peptide-based therapeutics. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials. Raghava, is an academic editor of PLoS ONE. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: One of the co-authors, Gajendra. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: All relevant data are within the paper and its Supporting Information files.įunding: Authors are thankful to funding agencies Council of Scientific and Industrial Research (project Open Source Drug Discovery and GENESIS BSC0121), Department of Science and Technology (DST INSPIRE) Govt. Received: JAccepted: ApPublished: June 1, 2018Ĭopyright: © 2018 Mathur et al. van Veen, University of Cambridge, UNITED KINGDOM In order to assist researchers in the prediction and designing of half-life of peptides, the models developed have been integrated into PlifePred web server ( ).Ĭitation: Mathur D, Singh S, Mehta A, Agrawal P, Raghava GPS (2018) In silico approaches for predicting the half-life of natural and modified peptides in blood. Thirdly, models were developed on 163 natural peptides using chemical descriptors and attained a maximum correlation of 0.743 using 45 selected PaDEL descriptors. Secondly, models were developed on 163 natural peptides using amino acid composition feature of peptides and achieved a maximum correlation of 0.643. The best model using 43 PaDEL descriptors got a maximum correlation of 0.692 between the predicted and the actual half-life peptides. Firstly, models have been developed on 261 peptides containing natural and modified residues, using different chemical descriptors. In this study, we used 163 natural and 98 modified peptides whose half-life has been determined experimentally in mammalian blood, for developing in silico models. This paper describes a web server developed for designing therapeutic peptides with desired half-life in blood.
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