title: Precisely Regulated and Efficient Locking of Linear Peptides into Stable Multicyclic Topologies through a One-Pot Reaction.
abstract: We report the discovery of a small phenyl molecule with four isosteric thiolate-reactive groups of sequentially varied reactivity. This molecule was exploited in combination with cysteine/penicillamine thiolates of different nucleophilic reactivity for precisely regulated and efficient locking (PROP-locking) of linear peptides into multicyclic topologies through a one-pot reaction. The PROP-locking relies on multistep and sequential thiolate/fluorine nucleophilic substitutions, which is not only rapid but highly specific, thus enabling rapid locking of peptides with high amino acid diversities without protecting groups. Several tricyclic peptide templates and bioactive peptides were designed and synthesized using the PROP-locking strategy. We believe that tricyclic peptides precisely locked through stable thioether bonds should be promising structurally constrained scaffolds for developing potential therapeutics and target ligands.
authors.affiliation: The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, State Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, P.R. China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Liu
authors.affiliation: The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, State Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials, 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: Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, 1015, Lausanne, Switzerland.
authors.forename: Xudong
authors.initials: X
authors.lastname: Kong
authors.affiliation: Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, 1015, Lausanne, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Heinis
authors.affiliation: The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, State Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials, 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, Collaborative Innovation Center of Chemistry for Energy Materials, 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: D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D010455:Peptides; D013438:Sulfhydryl Compounds
keywords: cyclization; cysteine; penicillamine; peptides; thioether bonds