title: Design, synthesis and biological evaluation of novel peptide MC2 analogues from Momordica charantia as potential anti-diabetic agents.
abstract: Three series of Momordica charantia (MC)2 analogues were designed, synthesized and evaluated for their anti-hyperglycaemic effects. Alanine scanning focusing on the peptide MC2 indicated the importance of the residues proline (Pro)(3), serine (Ser)(6), isoleucine (Ile)(7) and Ser(10) for anti-hyperglycaemic effects. Among the first series of MC2 analogues, peptide I-4 exhibited a better anti-hyperglycaemic effect and was chosen for further modification. A further two series of conformationally constrained analogues were designed by scanning the residues Pro(3), Ser(6), Ile(7), and Ser(10) with an i - (i + 2) lactam bridge consisting of a glutamic acid-Xaa-lysine (Glu-Xaa-Lys) scaffold and a diproline fragment. By screening in normal mice and mice with diabetes mellitus, peptides II-1, II-2 and III-3 showed a significant improvement in anti-hyperglycaemic and anti-oxidative activities compared with I-4. These data suggest that II-1, II-2 and III-3 could be candidates for 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. ydhuangwenlong@126.com.
authors.forename: Baowei
authors.initials: B
authors.lastname: Yang
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.forename: Chenyu
authors.initials: C
authors.lastname: Zhang
authors.forename: Sijia
authors.initials: S
authors.lastname: Yan
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Xuekun
authors.initials: X
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Deng
authors.forename: Hai
authors.initials: H
authors.lastname: Qian
authors.forename: Haiyan
authors.initials: H
authors.lastname: Lin
authors.forename: Wenlong
authors.initials: W
authors.lastname: Huang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D016207:Cytokines / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000737:chemistry* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D029777:Momordica charantia / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000737:chemistry* / Q000627:therapeutic use*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D007004:Hypoglycemic Agents; C506054:MC2 peptide; D010446:Peptide Fragments; D007371:Interferon-gamma