title: Design, synthesis and biological evaluation of novel peptide MC62 analogues as potential antihyperglycemic agents.
abstract: Two series of peptide MC62 analogues were synthesized, characterized and evaluated for their antihyperglycemic effects. Structure-activity relationship studies of the first series indicated that antihyperglycemic effects were correlated to residues 4, 5, 7 and 8. Peptide I-6 exhibited higher antihyperglycemic activity than the MC62 parent peptide, and was chosen for further modification. Incorporation of Met at position 3 increased potency further and generated II-3, which was screened in vivo and in vitro using exenatide (Ex-4) and GLP-1 as positive controls. The results showed that the antihyperglycemic and antioxidative activities of II-3 were comparable to the positive controls, suggesting II-3 could be a candidate for use as a future diabetic treatment.
authors.affiliation: Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu 210009, 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: Yicheng
authors.initials: Y
authors.lastname: Mei
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. Electronic address: qianhai24@163.com.
authors.forename: Hai
authors.initials: H
authors.lastname: Qian
authors.affiliation: Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu 210009, China. Electronic address: ydhuangwenlong@126.com.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Huang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis; D045744:Cell Line, Tumor; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy; D015195:Drug Design; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D018384:Oxidative Stress / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010455:Peptides
keywords: Antihyperglycemic; Antioxidative; Diabetes mellitus; MC62 peptide; Streptozotocin; Structure–activity relationship