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A Facile Procedure for One-Pot Stable Conjugation of Two Proglucagon Cysteine-Containing Peptide Analogs
Optimization of peptides for therapeutic purposes often includes chemical conjugation or modification with substituents that serve to broaden pharmacology or improve pharmacokinetics. We report a convenient and rapid procedure for one-pot, site-specific conjugation of two cysteine-containing peptide...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416343/ https://www.ncbi.nlm.nih.gov/pubmed/34484114 http://dx.doi.org/10.3389/fendo.2021.693958 |
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author | He, Rongjun Mowery, Stephanie A. Chabenne, Joseph Finan, Brian Mayer, John P. DiMarchi, Richard D. |
author_facet | He, Rongjun Mowery, Stephanie A. Chabenne, Joseph Finan, Brian Mayer, John P. DiMarchi, Richard D. |
author_sort | He, Rongjun |
collection | PubMed |
description | Optimization of peptides for therapeutic purposes often includes chemical conjugation or modification with substituents that serve to broaden pharmacology or improve pharmacokinetics. We report a convenient and rapid procedure for one-pot, site-specific conjugation of two cysteine-containing peptides that utilizes a bivalent linker comprising maleimide and iodoacetyl functional groups. Following maleimide-mediated peptide conjugation the linker was converted from an unstable thiosuccinimide to a stable thioether bond suitable for biological study by mild aqueous hydrolysis. The procedure is exemplified by peptide-peptide, peptide-small molecule, and peptide-fatty acid conjugations. The method provides a facile approach to search for enhanced biological outcomes through additive and sustained peptide pharmacology unencumbered by the prospect of chemical rearrangement in the course of biological study. |
format | Online Article Text |
id | pubmed-8416343 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84163432021-09-04 A Facile Procedure for One-Pot Stable Conjugation of Two Proglucagon Cysteine-Containing Peptide Analogs He, Rongjun Mowery, Stephanie A. Chabenne, Joseph Finan, Brian Mayer, John P. DiMarchi, Richard D. Front Endocrinol (Lausanne) Endocrinology Optimization of peptides for therapeutic purposes often includes chemical conjugation or modification with substituents that serve to broaden pharmacology or improve pharmacokinetics. We report a convenient and rapid procedure for one-pot, site-specific conjugation of two cysteine-containing peptides that utilizes a bivalent linker comprising maleimide and iodoacetyl functional groups. Following maleimide-mediated peptide conjugation the linker was converted from an unstable thiosuccinimide to a stable thioether bond suitable for biological study by mild aqueous hydrolysis. The procedure is exemplified by peptide-peptide, peptide-small molecule, and peptide-fatty acid conjugations. The method provides a facile approach to search for enhanced biological outcomes through additive and sustained peptide pharmacology unencumbered by the prospect of chemical rearrangement in the course of biological study. Frontiers Media S.A. 2021-08-18 /pmc/articles/PMC8416343/ /pubmed/34484114 http://dx.doi.org/10.3389/fendo.2021.693958 Text en Copyright © 2021 He, Mowery, Chabenne, Finan, Mayer and DiMarchi https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology He, Rongjun Mowery, Stephanie A. Chabenne, Joseph Finan, Brian Mayer, John P. DiMarchi, Richard D. A Facile Procedure for One-Pot Stable Conjugation of Two Proglucagon Cysteine-Containing Peptide Analogs |
title | A Facile Procedure for One-Pot Stable Conjugation of Two Proglucagon Cysteine-Containing Peptide Analogs |
title_full | A Facile Procedure for One-Pot Stable Conjugation of Two Proglucagon Cysteine-Containing Peptide Analogs |
title_fullStr | A Facile Procedure for One-Pot Stable Conjugation of Two Proglucagon Cysteine-Containing Peptide Analogs |
title_full_unstemmed | A Facile Procedure for One-Pot Stable Conjugation of Two Proglucagon Cysteine-Containing Peptide Analogs |
title_short | A Facile Procedure for One-Pot Stable Conjugation of Two Proglucagon Cysteine-Containing Peptide Analogs |
title_sort | facile procedure for one-pot stable conjugation of two proglucagon cysteine-containing peptide analogs |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416343/ https://www.ncbi.nlm.nih.gov/pubmed/34484114 http://dx.doi.org/10.3389/fendo.2021.693958 |
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