Back to Search
Start Over
oxSTEF Reagents Are Tunable and Versatile Electrophiles for Selective Disulfide-Rebridging of Native Proteins
- Source :
- Nisavic, M, Wørmer, G J, Nielsen, C S, Jeppesen, S M, Palmfeldt, J & Poulsen, T B 2023, ' oxSTEF Reagents Are Tunable and Versatile Electrophiles for Selective Disulfide-Rebridging of Native Proteins ', Bioconjugate Chemistry, vol. 34, no. 6, pp. 994-1003 . https://doi.org/10.1021/acs.bioconjchem.3c00005
- Publication Year :
- 2023
- Publisher :
- American Chemical Society (ACS), 2023.
-
Abstract
- Site-selective disulfide rebridging has emerged as a powerful strategy to modulate the structural and functional properties of proteins. Here, we introduce a novel class of electrophilic reagents, designated oxSTEF, that demonstrate excellent efficiency in disulfide rebridging via double thiol exchange. The oxSTEF reagents are prepared using an efficient synthetic sequence which may be diverted to obtain a range of derivatives allowing for tuning of reactivity or steric bulk. We demonstrate highly selective rebridging of cyclic peptides and native proteins, such as human growth hormone, and the absence of cross-reactivity with other nucleophilic amino acid residues. The oxSTEF conjugates undergo glutathione-mediated disintegration under tumor-relevant glutathione concentrations, which highlights their potential for use in targeted drug delivery. Finally, the α-dicarbonyl motif of the oxSTEF reagents enables "second phase" oxime ligation, which furthermore increases the thiol stability of the conjugates significantly.
Details
- ISSN :
- 15204812 and 10431802
- Database :
- OpenAIRE
- Journal :
- Bioconjugate Chemistry
- Accession number :
- edsair.doi.dedup.....ca80830788253294884664db53237ebb
- Full Text :
- https://doi.org/10.1021/acs.bioconjchem.3c00005