title: Design, synthesis, and biological evaluation of novel peptide Gly(3) -MC62 analogues as potential antidiabetic agents.
abstract: Two series of conformationally constrained analogues from Gly(3) -MC62 were designed by scanning the residues Lys(1) , Thr(2) , Met(4) , Lys(5) , Met(7,) and Ala(8) with an i-(i + 2) lactam bridge consisting of a Glutamic acid-xaa-lysine (Glu-Xaa-Lys) scaffold and a diproline fragment. They were synthesized and evaluated for their antihyperglycemic effects. Through screening in normal and mice with diabetes mellitus, peptides II-5, III-3, III-4, and III-5 showed significant improvement in antihyperglycemic and antioxidative activities compared with Gly(3) -MC62, especially the compound III-4. The primary mechanism of the compounds (II-5, III-3, III-4, and III-5) underlying this effect is the islet β-cells against oxidative damage induced by STZ, and III-4-treated mice showed considerable improvement in the preservation of beta cells in the pancreatic islets of DM mice. These data suggested that III-4 could be candidate for the future treatment of diabetes mellitus.
authors.affiliation: Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu, 210009, China.|Medical and Health Management Department, Jiangsu Food & Pharmaceutical Science College, 4 Meicheng Road, Higher Education Area, Huaian, Jiangsu, 223003, China.
authors.forename: Baowei
authors.initials: B
authors.lastname: Yang
authors.affiliation: Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu, 210009, China.
authors.forename: Chenyu
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu, 210009, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu, 210009, China.
authors.forename: Sijia
authors.initials: S
authors.lastname: Yan
authors.affiliation: Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu, 210009, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu, 210009, China.
authors.forename: Xuekun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu, 210009, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Deng
authors.affiliation: Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu, 210009, China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Huang
authors.affiliation: Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu, 210009, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Qian
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D055808:Drug Discovery; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D018384:Oxidative Stress / Q000187:drug effects; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010455:Peptides
keywords: antihyperglycemic; antioxidative; lactam bridge; peptide Gly3-MC62