title: Chiral Sulfoxide-Induced Single Turn Peptide α-Helicity.
abstract: Inducing α-helicity through side-chain cross-linking is a strategy that has been pursued to improve peptide conformational rigidity and bio-availability. Here we describe the preparation of small peptides tethered to chiral sulfoxide-containing macrocyclic rings. Furthermore, a study of structure-activity relationships (SARs) disclosed properties with respect to ring size, sulfur position, oxidation state, and stereochemistry that show a propensity to induce α-helicity. Supporting data include circular dichroism spectroscopy (CD), NMR spectroscopy, and a single crystal X-ray structure for one such stabilized peptide. Finally, theoretical studies are presented to elucidate the effect of chiral sulfoxides in inducing backbone α-helicity.
authors.affiliation: School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
authors.forename: Qingzhou
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Jiang
authors.affiliation: School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
authors.forename: Bingchuan
authors.initials: B
authors.lastname: Zhao
authors.affiliation: School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
authors.forename: Huacan
authors.initials: H
authors.lastname: Lin
authors.affiliation: School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.affiliation: School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Xie
authors.affiliation: Cardiovascular and Metabolic Diseases Medicinal Chemistry, Pfizer, Inc., 620 Memorial Drive, Cambridge, MA, 02142, USA.
authors.forename: Guoyun
authors.initials: G
authors.lastname: Bai
authors.affiliation: Cardiovascular and Metabolic Diseases Medicinal Chemistry, Pfizer, Inc., 620 Memorial Drive, Cambridge, MA, 02142, USA.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Gilbert
authors.affiliation: Cardiovascular and Metabolic Diseases Medicinal Chemistry, Pfizer, Inc., 620 Memorial Drive, Cambridge, MA, 02142, USA.
authors.forename: Gilles H
authors.initials: GH
authors.lastname: Goetz
authors.affiliation: Cardiovascular and Metabolic Diseases Medicinal Chemistry, Pfizer, Inc., 620 Memorial Drive, Cambridge, MA, 02142, USA.
authors.forename: Spiros
authors.initials: S
authors.lastname: Liras
authors.affiliation: Cardiovascular and Metabolic Diseases Medicinal Chemistry, Pfizer, Inc., 620 Memorial Drive, Cambridge, MA, 02142, USA.
authors.forename: Alan A
authors.initials: AA
authors.lastname: Mathiowetz
authors.affiliation: Cardiovascular and Metabolic Diseases Medicinal Chemistry, Pfizer, Inc., 620 Memorial Drive, Cambridge, MA, 02142, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.affiliation: Cardiovascular and Metabolic Diseases Medicinal Chemistry, Pfizer, Inc., 620 Memorial Drive, Cambridge, MA, 02142, USA.
authors.forename: Kun
authors.initials: K
authors.lastname: Song
authors.affiliation: Cardiovascular and Metabolic Diseases Medicinal Chemistry, Pfizer, Inc., 620 Memorial Drive, Cambridge, MA, 02142, USA.
authors.forename: Meihua
authors.initials: M
authors.lastname: Tu
authors.affiliation: Department of Biology, Southern University of Science and Technology, Shenzhen, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Wu
authors.affiliation: School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Center for Chemistry Innovation and Excellence, Pfizer Inc., Eastern Point Road, Groton, CT, 06340, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Flanagan
authors.affiliation: School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.|College of Chemistry, Peking University, Beijing, 100871, China.
authors.forename: Yun-Dong
authors.initials: YD
authors.lastname: Wu
authors.affiliation: School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
authors.forename: Zigang
authors.initials: Z
authors.lastname: Li
mesh_terms: D002942:Circular Dichroism; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry*; D000072756:Protein Conformation, alpha-Helical; D012451:Safrole / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D010455:Peptides; D012451:Safrole; C005746:sulfoxide