Multifunctional Scaffolds for Assembling Cancer-Targeting Immune Stimulators Using Chemoselective Ligations
Chemoselective ligations allow chemical biologists to functionalise proteins and peptides for biomedical applications and to probe biological processes. Coupled with solid phase peptide synthesis, chemoselective ligations enable not only the design of homogeneous proteins and peptides with desired n...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-03-01
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| Series: | Frontiers in Chemistry |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fchem.2019.00113/full |
| _version_ | 1818534712650498048 |
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| author | Anne C. Conibear Karine Thewes Nadja Groysbeck Christian F. W. Becker |
| author_facet | Anne C. Conibear Karine Thewes Nadja Groysbeck Christian F. W. Becker |
| author_sort | Anne C. Conibear |
| collection | DOAJ |
| description | Chemoselective ligations allow chemical biologists to functionalise proteins and peptides for biomedical applications and to probe biological processes. Coupled with solid phase peptide synthesis, chemoselective ligations enable not only the design of homogeneous proteins and peptides with desired natural and unnatural modifications in site-specific locations but also the design of new peptide and protein topologies. Although several well-established ligations are available, each method has its own advantages and disadvantages and they are seldom used in combination. Here we have applied copper-catalyzed azide-alkyne “click,” oxime, maleimide, and native chemical ligations to develop a modular synthesis of branched peptide and polymer constructs that act as cancer-targeting immune system engagers (ISErs) and functionalised them for detection in biological systems. We also note some potential advantages and pitfalls of these chemoselective ligations to consider when designing orthogonal ligation strategies. The modular synthesis and functionalization of ISErs facilitates optimisation of their activity and mechanism of action as potential cancer immunotherapies. |
| first_indexed | 2024-12-11T18:15:08Z |
| format | Article |
| id | doaj.art-3394c6db4cf8431aaecb7c61dd46eb32 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-11T18:15:08Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-3394c6db4cf8431aaecb7c61dd46eb322022-12-22T00:55:27ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462019-03-01710.3389/fchem.2019.00113438987Multifunctional Scaffolds for Assembling Cancer-Targeting Immune Stimulators Using Chemoselective LigationsAnne C. ConibearKarine ThewesNadja GroysbeckChristian F. W. BeckerChemoselective ligations allow chemical biologists to functionalise proteins and peptides for biomedical applications and to probe biological processes. Coupled with solid phase peptide synthesis, chemoselective ligations enable not only the design of homogeneous proteins and peptides with desired natural and unnatural modifications in site-specific locations but also the design of new peptide and protein topologies. Although several well-established ligations are available, each method has its own advantages and disadvantages and they are seldom used in combination. Here we have applied copper-catalyzed azide-alkyne “click,” oxime, maleimide, and native chemical ligations to develop a modular synthesis of branched peptide and polymer constructs that act as cancer-targeting immune system engagers (ISErs) and functionalised them for detection in biological systems. We also note some potential advantages and pitfalls of these chemoselective ligations to consider when designing orthogonal ligation strategies. The modular synthesis and functionalization of ISErs facilitates optimisation of their activity and mechanism of action as potential cancer immunotherapies.https://www.frontiersin.org/article/10.3389/fchem.2019.00113/fullligationclick chemistryorthogonal ligationsprotein conjugationpeptide functionalizationpeptide-polymer conjugates |
| spellingShingle | Anne C. Conibear Karine Thewes Nadja Groysbeck Christian F. W. Becker Multifunctional Scaffolds for Assembling Cancer-Targeting Immune Stimulators Using Chemoselective Ligations Frontiers in Chemistry ligation click chemistry orthogonal ligations protein conjugation peptide functionalization peptide-polymer conjugates |
| title | Multifunctional Scaffolds for Assembling Cancer-Targeting Immune Stimulators Using Chemoselective Ligations |
| title_full | Multifunctional Scaffolds for Assembling Cancer-Targeting Immune Stimulators Using Chemoselective Ligations |
| title_fullStr | Multifunctional Scaffolds for Assembling Cancer-Targeting Immune Stimulators Using Chemoselective Ligations |
| title_full_unstemmed | Multifunctional Scaffolds for Assembling Cancer-Targeting Immune Stimulators Using Chemoselective Ligations |
| title_short | Multifunctional Scaffolds for Assembling Cancer-Targeting Immune Stimulators Using Chemoselective Ligations |
| title_sort | multifunctional scaffolds for assembling cancer targeting immune stimulators using chemoselective ligations |
| topic | ligation click chemistry orthogonal ligations protein conjugation peptide functionalization peptide-polymer conjugates |
| url | https://www.frontiersin.org/article/10.3389/fchem.2019.00113/full |
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