title: Rethinking Cysteine Protective Groups: S-Alkylsulfonyl-l-Cysteines for Chemoselective Disulfide Formation.
abstract: The ability to reversibly cross-link proteins and peptides grants the amino acid cysteine its unique role in nature as well as in peptide chemistry. We report a novel class of S-alkylsulfonyl-l-cysteines and N-carboxy anhydrides (NCA) thereof for peptide synthesis. The S-alkylsulfonyl group is stable against amines and thus enables its use under Fmoc chemistry conditions and the controlled polymerization of the corresponding NCAs yielding well-defined homo- as well as block co-polymers. Yet, thiols react immediately with the S-alkylsulfonyl group forming asymmetric disulfides. Therefore, we introduce the first reactive cysteine derivative for efficient and chemoselective disulfide formation in synthetic polypeptides, thus bypassing additional protective group cleavage steps.
authors: Institute of Organic Chemistry, Johannes Gutenberg University Mainz, 55099, Mainz, Germany.
authors: Olga
authors: O
authors: Schäfer
authors: Institute of Organic Chemistry, Johannes Gutenberg University Mainz, 55099, Mainz, Germany.
authors: David
authors: D
authors: Huesmann
authors: Institute of Organic Chemistry, Johannes Gutenberg University Mainz, 55099, Mainz, Germany.
authors: Christian
authors: C
authors: Muhl
authors: Institute of Organic Chemistry, Johannes Gutenberg University Mainz, 55099, Mainz, Germany.
authors: Matthias
authors: http://orcid.org/0000-0002-1749-9034
authors: M
authors: Barz
mesh_terms: D000588:Amines; D000812:Anhydrides / Q000737:chemistry*; D003545:Cysteine / Q000737:chemistry*; D004220:Disulfides / Q000138:chemical synthesis / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D058105:Polymerization; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D000588:Amines; D000812:Anhydrides; D004220:Disulfides; D010455:Peptides; D013438:Sulfhydryl Compounds; D003545:Cysteine
keywords: S-alkylsulfonyl cysteine; drug delivery; peptides; protecting groups; ring-opening polymerization