title: Orthogonal Cysteine-Penicillamine Disulfide Pairing for Directing the Oxidative Folding of Peptides.
abstract: Precise disulfide pairing in synthetic peptides usually is achieved using orthogonal protecting group strategies or relies on primary sequence manipulation. Orthogonal disulfide pairing technology should be promising for directing the rational folding of multicyclic peptides from the fully reduced peptides. Here, we report a discovery on the orthogonality between heterodisulfide pairing of cysteine (Cys) and penicillamine (Pen) and formation of Cys-Cys/Pen-Pen homodisulfides. The orthogonal Cys-Pen disulfide pairing can be exploited for highly selective production of certain (multi)cyclic structures (or even a sole structure without isomers) through direct oxidation in air or thiol-disulfide exchanges in redox media. This strategy makes rational folding of multicyclic peptides without protecting groups, sequence manipulation, and complex synthetic reactions a reality, thus providing invaluable assets to peptide communities, and should greatly benefit the development of multicyclic peptide therapeutics and ligands.
authors.affiliation: The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen 361005, P. R. China.
authors.forename: Yiwu
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen 361005, P. R. China.
authors.forename: Linxiang
authors.initials: L
authors.lastname: Zhai
authors.affiliation: The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen 361005, P. R. China.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen 361005, P. R. China.
authors.forename: Chuanliu
authors.initials: C
authors.lastname: Wu
mesh_terms: D003545:Cysteine / Q000737:chemistry*; D010084:Oxidation-Reduction; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding
chemical_list: D010455:Peptides; C036069:penicillamine disulfide; D010396:Penicillamine; D003545:Cysteine