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Automated solid-phase peptide synthesis to obtain therapeutic peptides
The great versatility and the inherent high affinities of peptides for their respective targets have led to tremendous progress for therapeutic applications in the last years. In order to increase the drugability of these frequently unstable and rapidly cleared molecules, chemical modifications are...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Beilstein-Institut
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077397/ https://www.ncbi.nlm.nih.gov/pubmed/24991269 http://dx.doi.org/10.3762/bjoc.10.118 |
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author | Mäde, Veronika Els-Heindl, Sylvia Beck-Sickinger, Annette G |
author_facet | Mäde, Veronika Els-Heindl, Sylvia Beck-Sickinger, Annette G |
author_sort | Mäde, Veronika |
collection | PubMed |
description | The great versatility and the inherent high affinities of peptides for their respective targets have led to tremendous progress for therapeutic applications in the last years. In order to increase the drugability of these frequently unstable and rapidly cleared molecules, chemical modifications are of great interest. Automated solid-phase peptide synthesis (SPPS) offers a suitable technology to produce chemically engineered peptides. This review concentrates on the application of SPPS by Fmoc/t-Bu protecting-group strategy, which is most commonly used. Critical issues and suggestions for the synthesis are covered. The development of automated methods from conventional to essentially improved microwave-assisted instruments is discussed. In order to improve pharmacokinetic properties of peptides, lipidation and PEGylation are described as covalent conjugation methods, which can be applied by a combination of automated and manual synthesis approaches. The synthesis and application of SPPS is described for neuropeptide Y receptor analogs as an example for bioactive hormones. The applied strategies represent innovative and potent methods for the development of novel peptide drug candidates that can be manufactured with optimized automated synthesis technologies. |
format | Online Article Text |
id | pubmed-4077397 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Beilstein-Institut |
record_format | MEDLINE/PubMed |
spelling | pubmed-40773972014-07-02 Automated solid-phase peptide synthesis to obtain therapeutic peptides Mäde, Veronika Els-Heindl, Sylvia Beck-Sickinger, Annette G Beilstein J Org Chem Review The great versatility and the inherent high affinities of peptides for their respective targets have led to tremendous progress for therapeutic applications in the last years. In order to increase the drugability of these frequently unstable and rapidly cleared molecules, chemical modifications are of great interest. Automated solid-phase peptide synthesis (SPPS) offers a suitable technology to produce chemically engineered peptides. This review concentrates on the application of SPPS by Fmoc/t-Bu protecting-group strategy, which is most commonly used. Critical issues and suggestions for the synthesis are covered. The development of automated methods from conventional to essentially improved microwave-assisted instruments is discussed. In order to improve pharmacokinetic properties of peptides, lipidation and PEGylation are described as covalent conjugation methods, which can be applied by a combination of automated and manual synthesis approaches. The synthesis and application of SPPS is described for neuropeptide Y receptor analogs as an example for bioactive hormones. The applied strategies represent innovative and potent methods for the development of novel peptide drug candidates that can be manufactured with optimized automated synthesis technologies. Beilstein-Institut 2014-05-22 /pmc/articles/PMC4077397/ /pubmed/24991269 http://dx.doi.org/10.3762/bjoc.10.118 Text en Copyright © 2014, Mäde et al. https://creativecommons.org/licenses/by/2.0https://www.beilstein-journals.org/bjoc/termsThis is an Open Access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (https://www.beilstein-journals.org/bjoc/terms) |
spellingShingle | Review Mäde, Veronika Els-Heindl, Sylvia Beck-Sickinger, Annette G Automated solid-phase peptide synthesis to obtain therapeutic peptides |
title | Automated solid-phase peptide synthesis to obtain therapeutic peptides |
title_full | Automated solid-phase peptide synthesis to obtain therapeutic peptides |
title_fullStr | Automated solid-phase peptide synthesis to obtain therapeutic peptides |
title_full_unstemmed | Automated solid-phase peptide synthesis to obtain therapeutic peptides |
title_short | Automated solid-phase peptide synthesis to obtain therapeutic peptides |
title_sort | automated solid-phase peptide synthesis to obtain therapeutic peptides |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077397/ https://www.ncbi.nlm.nih.gov/pubmed/24991269 http://dx.doi.org/10.3762/bjoc.10.118 |
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