Cyclic Thiosulfinates as a Novel Class of Disulfide Cleavable Cross-Linkers for Rapid Hydrogel Synthesis.

Autor:	Aluri KC; Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States.; Barnett Institute of Chemical and Biological Analysis, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States., Hossain MA; Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States.; Barnett Institute of Chemical and Biological Analysis, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States., Kanetkar N; Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States., Miller BC; Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States., Dowgiallo MG; Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States., Sivasankar D; Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States.; Barnett Institute of Chemical and Biological Analysis, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States., Sullivan MR; Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States., Manetsch R; Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States.; Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States., Konry T; Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States., Ekenseair A; Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States., Agar JN; Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States.; Barnett Institute of Chemical and Biological Analysis, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States.; Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, United States.
Jazyk:	angličtina
Zdroj:	Bioconjugate chemistry [Bioconjug Chem] 2021 Mar 17; Vol. 32 (3), pp. 584-594. Date of Electronic Publication: 2021 Feb 19.
DOI:	10.1021/acs.bioconjchem.1c00049
Abstrakt:	We recently reported that cyclic thiosulfinates are cysteine selective cross-linkers that avoid the "dead-end" modifications that contribute to other cross-linkers' toxicity. In this study, we generalize the chemistry of cyclic thiosulfinates to that of thiol selective cross-linking and apply them to the synthesis of hydrogels. Thiol-functionalized four-arm poly(ethylene glycol) and hyaluronic acid monomers were cross-linked with 1,2-dithiane-1-oxide to form disulfide cross-linked hydrogels within seconds. The synthesized hydrogel could be reduced with physiological concentrations of glutathione, which modulated hydrogel mechanical properties and degradation kinetics. Bovine serum albumin protein was successfully encapsulated in hydrogel, and diffusion-mediated release was demonstrated in vitro. Hep G2 cells grew in the presence of preformed hydrogel and during hydrogel synthesis, demonstrating acceptable cytotoxicity. We encapsulated cells within a hydrogel and demonstrated cell growth and recovery up to 10 days, with and without cell adhesion peptides. In summary, we report cyclic thiosulfinates as a novel class of cross-linkers for the facile synthesis of biodegradable hydrogels.
Databáze:	MEDLINE
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