Sulfonate Version of OHPAS Linker Has Two Distinct Pathways of Breakdown: Elimination Route Allows Para-Hydroxy-Protected Benzylsulfonate (PHP-BS) to Serve as an Alternative Self-Immolative Group
| Autor: | Jina Song, Hyang Sook Lee, Beomseok Seo, Sun-Young Kim, Suho Park, Donghoon Seo, Okku Park, Doohwan Jung, Jongun Cho, Sanghyeon Yun, Jaeho Lee, Ha Jihyeon, Sangkwang Lee, Minah Seol, Tae Kyo Park, Kim Sena |
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| Rok vydání: | 2020 |
| Předmět: |
Stereochemistry
Biomedical Engineering Pharmaceutical Science Bioengineering 02 engineering and technology 01 natural sciences Mice chemistry.chemical_compound Drug Stability Group (periodic table) Prohibitins Animals Humans Mesylates Pharmacology Drug Carriers 010405 organic chemistry Aryl Organic Chemistry technology industry and agriculture 021001 nanoscience & nanotechnology 0104 chemical sciences Drug Liberation Sulfonate chemistry Cyclization Human plasma 0210 nano-technology Linker Biotechnology Conjugate |
| Zdroj: | Bioconjugate Chemistry. 31:1392-1399 |
| ISSN: | 1520-4812 1043-1802 |
| Popis: | Recently we have reported that the ortho-hydroxy-protected aryl sulfate (OHPAS) system can be exploited as a new self-immolative group (SIG) for phenolic payloads. We extended the system to nonphenolic payloads by simply introducing a para-hydroxy benzyl (PHB) spacer. As an additional variation of the system, we explored a benzylsulfonate version of the OHPAS system and found that it has two distinct breakdown pathways, cyclization and 1,4-elimination, the latter of which implies that para-hydroxy-protected (PHP) benzylsulfonate (BS) can also be used as an alternative SIG. The PHP-BS system was found to be stable chemically and in mouse and human plasma, having payload release rates comparable to those of the original OHPAS conjugates. |
| Databáze: | OpenAIRE |
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