Estimating peptide half‐life in serum from tunable, sequence‐related physicochemical properties

Detalhes bibliográficos
Autor(a) principal: Cavaco, Marco
Data de Publicação: 2021
Outros Autores: Valle, Javier, Flores, Isabel, Andreu, David, Castanho, Miguel A. R. B.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/46930
Resumo: © 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
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spelling Estimating peptide half‐life in serum from tunable, sequence‐related physicochemical properties© 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.Proteolytic instability is a critical limitation for peptide-based products. Although significant efforts are devoted to stabilize sequences against proteases/peptidases in plasma/serum, such approaches tend to be rather empirical, unspecific, time-consuming, and frequently not cost-effective. A more rational and potentially rewarding alternative is to identify the chemical grounds of susceptibility to enzymatic degradation of peptides so that proteolytic resistance can be tuned by manipulation of key chemical properties. In this regard, we conducted a meta-analysis of literature published over the last decade reporting experimental data on the lifetimes of peptides exposed to proteolytic conditions. Our initial database contained 579 entries and was curated with regard to amino acid sequence, chemical modification, terminal half-life (t1/2 ) or other stability readouts, type of stability assay, and biological application of the study. Although the majority of entries in the database corresponded to (slightly or substantially) modified peptides, we chose to focus on unmodified ones, as we aimed to decipher intrinsic characteristics of peptide proteolytic susceptibility. Specifically, we developed a multivariable regression model to unravel those peptide properties with most impact on proteolytic stability and thus potential t1/2 predicting ability. Model validation was done by two different approaches. First, a library of peptides spanning a large interval of properties that modulate stability was synthesized and their t1/2 in human serum were experimentally determined. Second, the t1/2 of 21 selected peptides approved for clinical use or in clinical trials were recorded and matched with the model-estimated values. With both approaches, good correlation between experimental and predicted t1/2 data was observed.This research was supported by the Portuguese Fundação para a Ciência e a Tecnologia (FCT; grants PD/BD/128281/2017, PTDC/BBB- NAN/1578/2014, PTDC/BIA- VIR/29495/2017, UID/Multi/04349/2019, and PTDC/QUI- NUC/30147/2017), the Spanish Ministry of Economy and Innovation (MINECO, grants AGL2014- 52395- C2- 2- R and AGL2017- 84097- C2- 2- R, and Maria de Maeztu Program for Centers of Excellence); the European Union H2020- MSCA- RISE- 2014 program (grant no. 828774), and the “La Caixa” Banking Foundation (grant HR17- 00409)John Wiley & Sons, Inc.Repositório da Universidade de LisboaCavaco, MarcoValle, JavierFlores, IsabelAndreu, DavidCastanho, Miguel A. R. B.2021-03-19T16:23:16Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/46930engClin Transl Sci. 2021 Feb 28.1752-805410.1111/cts.129851752-8062info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:49:30Zoai:repositorio.ul.pt:10451/46930Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:58:59.862635Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Estimating peptide half‐life in serum from tunable, sequence‐related physicochemical properties
title Estimating peptide half‐life in serum from tunable, sequence‐related physicochemical properties
spellingShingle Estimating peptide half‐life in serum from tunable, sequence‐related physicochemical properties
Cavaco, Marco
title_short Estimating peptide half‐life in serum from tunable, sequence‐related physicochemical properties
title_full Estimating peptide half‐life in serum from tunable, sequence‐related physicochemical properties
title_fullStr Estimating peptide half‐life in serum from tunable, sequence‐related physicochemical properties
title_full_unstemmed Estimating peptide half‐life in serum from tunable, sequence‐related physicochemical properties
title_sort Estimating peptide half‐life in serum from tunable, sequence‐related physicochemical properties
author Cavaco, Marco
author_facet Cavaco, Marco
Valle, Javier
Flores, Isabel
Andreu, David
Castanho, Miguel A. R. B.
author_role author
author2 Valle, Javier
Flores, Isabel
Andreu, David
Castanho, Miguel A. R. B.
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Cavaco, Marco
Valle, Javier
Flores, Isabel
Andreu, David
Castanho, Miguel A. R. B.
description © 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
publishDate 2021
dc.date.none.fl_str_mv 2021-03-19T16:23:16Z
2021
2021-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/46930
url http://hdl.handle.net/10451/46930
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Clin Transl Sci. 2021 Feb 28.
1752-8054
10.1111/cts.12985
1752-8062
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv John Wiley & Sons, Inc.
publisher.none.fl_str_mv John Wiley & Sons, Inc.
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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