Cargando…
Exploring the Chemical Properties and Medicinal Applications of Tetramethylthiocycloheptyne Sulfoximine Used in Strain-Promoted Azide–Alkyne Cycloaddition Reactions
The recently developed compound, tetramethylthiocycloheptyne sulfoximine (TMTHSI), has shown to be a promising strained alkyne for strain-promoted azide–alkyne cycloaddition (SPAAC), metal-free click chemistry. This research explores the properties of TMTHSI-based compounds via three aspects: (1) la...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10459143/ https://www.ncbi.nlm.nih.gov/pubmed/37631074 http://dx.doi.org/10.3390/ph16081155 |
_version_ | 1785097338878951424 |
---|---|
author | Timmers, Matt Kipper, Andi Frey, Raphael Notermans, Stef Voievudskyi, Maksym Wilson, Claire Hentzen, Nina Ringle, Michael Bovino, Clara Stump, Bernhard Rijcken, Cristianne J. F. Vermonden, Tina Dijkgraaf, Ingrid Liskamp, Rob |
author_facet | Timmers, Matt Kipper, Andi Frey, Raphael Notermans, Stef Voievudskyi, Maksym Wilson, Claire Hentzen, Nina Ringle, Michael Bovino, Clara Stump, Bernhard Rijcken, Cristianne J. F. Vermonden, Tina Dijkgraaf, Ingrid Liskamp, Rob |
author_sort | Timmers, Matt |
collection | PubMed |
description | The recently developed compound, tetramethylthiocycloheptyne sulfoximine (TMTHSI), has shown to be a promising strained alkyne for strain-promoted azide–alkyne cycloaddition (SPAAC), metal-free click chemistry. This research explores the properties of TMTHSI-based compounds via three aspects: (1) large-scale production, (2) unique stability in acidic conditions and its subsequent use in peptide synthesis, and (3) the functionalization of antibodies. Here, it is shown that (1) scale-up is achieved on a scale of up to 100 g. (2) TMTHSI is remarkably stable against TFA allowing for the site-specific functionalization of peptides on resin. Finally, (3) the functionalization of an antibody with a model payload is very efficient, with antibody conjugation demonstrating more beneficial features such as a high yield and limited hydrophobicity as compared to other alkyne reagent conjugates. These results illustrate the high potential of TMTHSI for diverse bioconjugation applications, with production already being GMP-compatible and a highly efficient conversion resulting in attractive costs of goods. |
format | Online Article Text |
id | pubmed-10459143 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-104591432023-08-27 Exploring the Chemical Properties and Medicinal Applications of Tetramethylthiocycloheptyne Sulfoximine Used in Strain-Promoted Azide–Alkyne Cycloaddition Reactions Timmers, Matt Kipper, Andi Frey, Raphael Notermans, Stef Voievudskyi, Maksym Wilson, Claire Hentzen, Nina Ringle, Michael Bovino, Clara Stump, Bernhard Rijcken, Cristianne J. F. Vermonden, Tina Dijkgraaf, Ingrid Liskamp, Rob Pharmaceuticals (Basel) Article The recently developed compound, tetramethylthiocycloheptyne sulfoximine (TMTHSI), has shown to be a promising strained alkyne for strain-promoted azide–alkyne cycloaddition (SPAAC), metal-free click chemistry. This research explores the properties of TMTHSI-based compounds via three aspects: (1) large-scale production, (2) unique stability in acidic conditions and its subsequent use in peptide synthesis, and (3) the functionalization of antibodies. Here, it is shown that (1) scale-up is achieved on a scale of up to 100 g. (2) TMTHSI is remarkably stable against TFA allowing for the site-specific functionalization of peptides on resin. Finally, (3) the functionalization of an antibody with a model payload is very efficient, with antibody conjugation demonstrating more beneficial features such as a high yield and limited hydrophobicity as compared to other alkyne reagent conjugates. These results illustrate the high potential of TMTHSI for diverse bioconjugation applications, with production already being GMP-compatible and a highly efficient conversion resulting in attractive costs of goods. MDPI 2023-08-15 /pmc/articles/PMC10459143/ /pubmed/37631074 http://dx.doi.org/10.3390/ph16081155 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Timmers, Matt Kipper, Andi Frey, Raphael Notermans, Stef Voievudskyi, Maksym Wilson, Claire Hentzen, Nina Ringle, Michael Bovino, Clara Stump, Bernhard Rijcken, Cristianne J. F. Vermonden, Tina Dijkgraaf, Ingrid Liskamp, Rob Exploring the Chemical Properties and Medicinal Applications of Tetramethylthiocycloheptyne Sulfoximine Used in Strain-Promoted Azide–Alkyne Cycloaddition Reactions |
title | Exploring the Chemical Properties and Medicinal Applications of Tetramethylthiocycloheptyne Sulfoximine Used in Strain-Promoted Azide–Alkyne Cycloaddition Reactions |
title_full | Exploring the Chemical Properties and Medicinal Applications of Tetramethylthiocycloheptyne Sulfoximine Used in Strain-Promoted Azide–Alkyne Cycloaddition Reactions |
title_fullStr | Exploring the Chemical Properties and Medicinal Applications of Tetramethylthiocycloheptyne Sulfoximine Used in Strain-Promoted Azide–Alkyne Cycloaddition Reactions |
title_full_unstemmed | Exploring the Chemical Properties and Medicinal Applications of Tetramethylthiocycloheptyne Sulfoximine Used in Strain-Promoted Azide–Alkyne Cycloaddition Reactions |
title_short | Exploring the Chemical Properties and Medicinal Applications of Tetramethylthiocycloheptyne Sulfoximine Used in Strain-Promoted Azide–Alkyne Cycloaddition Reactions |
title_sort | exploring the chemical properties and medicinal applications of tetramethylthiocycloheptyne sulfoximine used in strain-promoted azide–alkyne cycloaddition reactions |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10459143/ https://www.ncbi.nlm.nih.gov/pubmed/37631074 http://dx.doi.org/10.3390/ph16081155 |
work_keys_str_mv | AT timmersmatt exploringthechemicalpropertiesandmedicinalapplicationsoftetramethylthiocycloheptynesulfoximineusedinstrainpromotedazidealkynecycloadditionreactions AT kipperandi exploringthechemicalpropertiesandmedicinalapplicationsoftetramethylthiocycloheptynesulfoximineusedinstrainpromotedazidealkynecycloadditionreactions AT freyraphael exploringthechemicalpropertiesandmedicinalapplicationsoftetramethylthiocycloheptynesulfoximineusedinstrainpromotedazidealkynecycloadditionreactions AT notermansstef exploringthechemicalpropertiesandmedicinalapplicationsoftetramethylthiocycloheptynesulfoximineusedinstrainpromotedazidealkynecycloadditionreactions AT voievudskyimaksym exploringthechemicalpropertiesandmedicinalapplicationsoftetramethylthiocycloheptynesulfoximineusedinstrainpromotedazidealkynecycloadditionreactions AT wilsonclaire exploringthechemicalpropertiesandmedicinalapplicationsoftetramethylthiocycloheptynesulfoximineusedinstrainpromotedazidealkynecycloadditionreactions AT hentzennina exploringthechemicalpropertiesandmedicinalapplicationsoftetramethylthiocycloheptynesulfoximineusedinstrainpromotedazidealkynecycloadditionreactions AT ringlemichael exploringthechemicalpropertiesandmedicinalapplicationsoftetramethylthiocycloheptynesulfoximineusedinstrainpromotedazidealkynecycloadditionreactions AT bovinoclara exploringthechemicalpropertiesandmedicinalapplicationsoftetramethylthiocycloheptynesulfoximineusedinstrainpromotedazidealkynecycloadditionreactions AT stumpbernhard exploringthechemicalpropertiesandmedicinalapplicationsoftetramethylthiocycloheptynesulfoximineusedinstrainpromotedazidealkynecycloadditionreactions AT rijckencristiannejf exploringthechemicalpropertiesandmedicinalapplicationsoftetramethylthiocycloheptynesulfoximineusedinstrainpromotedazidealkynecycloadditionreactions AT vermondentina exploringthechemicalpropertiesandmedicinalapplicationsoftetramethylthiocycloheptynesulfoximineusedinstrainpromotedazidealkynecycloadditionreactions AT dijkgraafingrid exploringthechemicalpropertiesandmedicinalapplicationsoftetramethylthiocycloheptynesulfoximineusedinstrainpromotedazidealkynecycloadditionreactions AT liskamprob exploringthechemicalpropertiesandmedicinalapplicationsoftetramethylthiocycloheptynesulfoximineusedinstrainpromotedazidealkynecycloadditionreactions |