GIP(Lys16PAL) and GIP(Lys37PAL): Novel long-acting acylated analogues of glucose-dependent insulinotropic polypeptide with improved antidiabetic potential

Journal of Medicinal Chemistry

Volumn 49, Issue 3, 2006, Pages 1047-1054

  Irwin, Nigel ^e   O'Harte, Finbarr P M ^a   Gault, Victor A ^a   Green, Brian D ^a   Greer, Brett ^b   Harriott, Patrick ^c   Bailey, Clifford J ^d   Flatt, Peter R ^a  

^a UNIVERSITY OF ULSTER   (United Kingdom)

^b QUEEN'S UNIVERSITY BELFAST   (United Kingdom)

^c ROYAL COLLEGE OF SURGEONS IN IRELAND   (Ireland)

^d ASTON UNIVERSITY   (United Kingdom)

^e NONE

Author keywords

[No Author keywords available]

Indexed keywords

ALBUGON; CYCLIC AMP; DIPEPTIDYL PEPTIDASE IV; EXENDIN 4; FATTY ACID; GASTRIC INHIBITORY POLYPEPTIDE; GASTRIC INHIBITORY POLYPEPTIDE DERIVATIVE; GLUCAGON LIKE PEPTIDE 1 DERIVATIVE; GLUCOSE; LIRAGLUTIDE; UNCLASSIFIED DRUG; ANTIDIABETIC AGENT; GLUCOSE DEPENDENT INSULINOTROPIC POLYPEPTIDE, EPSILON PALMITOYL LYS(16); GLUCOSE DEPENDENT INSULINOTROPIC POLYPEPTIDE, EPSILON PALMITOYL LYS(37); GLUCOSE-DEPENDENT INSULINOTROPIC POLYPEPTIDE, EPSILON-PALMITOYL-LYS(16)-; GLUCOSE-DEPENDENT INSULINOTROPIC POLYPEPTIDE, EPSILON-PALMITOYL-LYS(37)-; INSULIN; SERUM ALBUMIN;

ADOLESCENT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DERIVATIZATION; DOSE RESPONSE; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG SYNTHESIS; GLUCOSE TOLERANCE; IN VITRO STUDY; IN VIVO STUDY; INSULIN RELEASE; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; RECEPTOR UPREGULATION; AMINO ACID SEQUENCE; ANIMAL; BIOSYNTHESIS; BLOOD; CHEMISTRY; CRICETULUS; DRUG EFFECT; FIBROBLAST; GLUCOSE BLOOD LEVEL; GLUCOSE TOLERANCE TEST; HAMSTER; HYDROLYSIS; MASS SPECTROMETRY; METABOLISM; MOLECULAR GENETICS; MOUSE MUTANT; PROTEIN BINDING; SECRETION; STRUCTURE ACTIVITY RELATION; SYNTHESIS; TIME;

AMINO ACID SEQUENCE; ANIMALS; ANTIGENS, CD26; BLOOD GLUCOSE; CRICETINAE; CRICETULUS; CYCLIC AMP; FIBROBLASTS; GASTRIC INHIBITORY POLYPEPTIDE; GLUCOSE TOLERANCE TEST; HYDROLYSIS; HYPOGLYCEMIC AGENTS; INSULIN; MICE; MICE, OBESE; MOLECULAR SEQUENCE DATA; PROTEIN BINDING; SERUM ALBUMIN; SPECTROMETRY, MASS, MATRIX-ASSISTED LASER DESORPTION-IONIZATION; STRUCTURE-ACTIVITY RELATIONSHIP; TIME FACTORS;

EID: 32344432601     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0509997     Document Type: Article

References (49)

1. Brown, J. C. Enteroinsular axis. In Gut Peptides: Biochemistry and Physiology; Dockray, G. J., Walsh, J. H., Eds.; Raven Press: New York, 1994; pp 765-784.
2. Gault, V. A.; Flatt, P. R.; O'Harte, F. P. M. Glucose-dependent insulinotropic polypeptide analogues and their therapeutic potential for the treatment of obesity-diabetes. Biochem. Biophys. Res. Commun. 2003, 308, 207-213.
3. Meier, J. J.; Nauck, M. A.; Schmidt, W. E.; Gallwitz, B. Gastric inhibitory polypeptide: the neglected incretin revisited. Regul. Pept. 2002, 107, 1-13.
4. Bailey, C. J.; Flatt, P. R. Development of antidiabetic drugs. In Drugs, diet and disease: mechanistic approaches to diabetes; Ioannides, C., Flatt, P. R., Eds.; Ellis Horwood: London, 1995; pp 279-326.
5. Mentlein, R. Dipeptidyl-peptidase IV (CD26) - role in the inactivation of regulatory peptides. Regul. Pept. 1999, 85, 9-24.
6. Kieffer, T. J.; McIntosh, C. H. S.; Pederson, R. A. Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV. Endocrinology 1995, 136, 3585-3596.
7. Schmidt, W. E.; Siegel, E. G.; Kümmel, H.; Gallwitz, B.; Creutzfeldt, W. Commercially available preparations of porcine glucose-dependent insulinotropic polypeptide (GIP) contain a biologically inactive GIP-fragment and cholecystokinin-33/-39. Endocrinology 1987, 120, 835-837.
8. Gault, V. A.; Parker, J. C.; Harriott, P.; Flatt, P. R.; O'Harte, F. P. M. Evidence that the major degradation product of glucose-dependent insulinotropic polypeptide (GIP), GIP(3-42), is a GIP receptor antagonist in vivo. J. Endocrinol. 2002, 175, 525-553.
9. O'Harte, F. P. M.; Mooney, M. H.; Kelly, C. M. N.; Flatt, P. R. Improved glycaemic control in obese diabetic ob/ob mice using N-terminally modified gastric inhibitory polypeptide. J. Endocrinol. 2000, 165, 639-648.
10. O'Harte, F. P. M.; Gault, V. A.; Parker, J. C.; Harriott, P.; Mooney, M. H.; Bailey, C. J.; Flatt, P. R. Improved stability, insulin-releasing activity and antidiabetic potential of two novel N-terminal analogues of glucose-dependent insulinotropic polypeptide: N-acetyl-GIP and pGlu-GIP. Diabetologia 2002, 45, 1281-1291.
11. 1-modified enzyme resistant forms of GIP, is associated with significant antihyperglycaemic activity in spontaneous obesity-diabetes. Biochem. J. 2002, 367, 913-920.
12. 2-substituted analogues of glucose-dependent insulinotropic polypeptide. J. Endocrinol. 2003, 176, 133-141.
13. 2]glucose-dependent insulinotropic polypeptide (GIP) improves glucose tolerance in normal and obese diabetic rats. Diabetes 2002, 51, 656-661.
14. Lindsay, J. R.; Au, S. T. B.; Kelly, C. M. N.; O'Harte, F. P. M.; Flatt, P. R. A novel amino-terminally glycated analogue of glucose-dependent insulinotropic polypeptide (GIP), with a prolonged insulinotropic activity in type 2 diabetes mellitus. Diabetes 2002, 51, 1394 (Abstract).
15. Elahi, D.; McAloon-Dyke, M.; Kukagawa, N. K.; Meneilly, G. S.; Slater, A. L.; Minaker, K. L.; Habener, J. F.; Andersen, D. K. The insulinotropic actions of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7-37) in normal and diabetic subjects. Regul Pept. 1994, 51, 63-74.
16. Nauck, M. A.; Bartels, E.; Ørskov, C.; Ebert, R.; Creutzfeldt, W. Additive insulinotropic effects of exogenous synthetic human gastric inhibitory polypeptide and glucagon-like peptide-1-(7-36) amide infused at near physiological insulinotropic hormone and glucose concentrations. J. Clin. Endocrinol. Metab. 1993, 76, 912-917.
17. Vilsboll, T.; Krarup, T.; Madsbad, S.; Holst, J. J. Defective amplification of the late phase insulin response to glucose by GIP in obese Type II diabetic patients. Diabetologia 2002, 45, 1111-1119.
18. Krarup, T.; Saurbrey, N.; Moody, A. J.; Kuhl, C.; Madsbad, S. Effect of porcine gastric inhibitory polypeptide on beta-cell function in type I and type II diabetes mellitus. Metabolism 1987, 36, 677-682.
19. Meier, J. J.; Gallwitz, B.; Kask, B.; Deacon, C. F.; Holst, J. J.; Schmidt, W. E.; Nauck, M. A. Stimulation of insulin secretion by intravenous bolus injection and continuous infusion of gastric inhibitory polypeptide in patients with type 2 diabetes and healthy control subjects. Diabetes 2004, 53, S220-224.
20. Meier, J. J.; Nauck, M. A.; Siepmann, N.; Greulich, M.; Holst, J. J.; Deacon, C. F.; Schmidt, W. E.; Gallwitz, B. Similar insulin secretory response to a gastric inhibitory polypeptide bolus injection at euglycemia in first-degree relatives of patients with type 2 diabetes and control subjects. Metabolism 2003, 52, 1579-1585.
21. Meier, J. J.; Nauck, M. A.; Kranz, D.; Holst, J. J.; Deacon, C. F.; Gaeckler, D.; Schmidt, W. E.; Gallwitz, B. Secretion, degradation, and elimination of glucagon-like peptide 1 and gastric inhibitory polypeptide in patients with chronic renal insufficiency and healthy control subjects. Diabetes 2004, 53, 654-662.
22. Kurtzhals, P.; Havelund, S.; Jonassen, I.; Kiehr, B.; Larsen, U. D.; Ribel, U.; Markussen, J. Albumin binding of insulins acylated with fatty acids: characterisation of the ligand-protein interaction and correlation between binding affinity and timing of the insulin effect in vivo. Biochem. J. 1995, 312, 725-731.
23. Agersø, H.; Jensen, L. B.; Elbrønd, B.; Rolan, P.; Zdravkovic, M. The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy man. Diabetologia 2002, 45, 195-202.
24. (a) Ribel, U.; Larsen, M. O.; Rolin, B.; Carr, R. D.; Wilken, M.; Sturis, J.; Westergaard, L.; Deacon, C. F.; Knudsen, L. B. NN2211: a long-acting glucagon-like peptide-1 derivative with antidiabetic effects in glucose-intolerant pigs. Eur. J. Pharm. 2002, 451, 217-225.
25. (b) Nauck, M. A.; Niederereichholz, U.; Ettler, R.; Holst, J. J.; Ørskov, C.; Ritzel, R.; Schmigel, W. H. Glucagon-like peptide-1 inhibition of gastric-emptying outweighs its insulinotropic effects in healthy humans. Am. J. Physiol. 1997, 273, E981-E988.
26. Ahren, B.; Schmitz, O. GLP-1 receptor agonists and DPP-4 inhibitors in the treatment of type 2 diabetes. Horm. Metab. Res. 2004, 36, 867-76.
27. Nauck, M. A.; Meier, J. J. Glucagon-like peptide 1 and its derivatives in the treatment of diabetes. Regul. Pept. 2005, 128, 135-148.
28. Meier, J. J.; Goetze, O.; Anstipp, J.; Hagemann, D.; Holst, J. J.; Schmidt, W. E.; Gallwitz, B.; Nauck, M. A. Gastric inhibitory polypeptide (GIP) does not inhibit gastric emptying in man. Am. J. Physiol. Endocrinol. Metab. 2003, 286, E621-E625.
29. 37). Biol. Chem. 2005, 386, 679-687.
30. Irwin, N.; Green, B. D.; Mooney, M. H.; Greer, B.; Harriott, P.; Bailey, C. J.; Gault, V. A.; O'Harte, F. P. M.; Flatt, P. R. A novel, long-acting agonist of GIP suitable for once daily administration in type 2 diabetes. J. Pharm. Exp. Ther. 2005, 314, 1187-1194.
31. Irwin, N.; Green, B. D.; Gault, V. A.; Greer, B.; Harriott, P.; Bailey, C. J.; Flatt, P. R.; O'Harte, F. P. M. Degradation, insulin secretion and antihyperglycaemic actions of two palmitate-derivitised N-terminal pyroglutamyl analogues of glucose-dependent insulinotropic polypeptide (GIP). J. Med. Chem. 2005, 48, 1244-1250.
32. Gault, V. A.; O'Harte, F. P. M.; Flatt, P. R. Glucose-dependent insulinotropic polypeptide (GIP): anti-diabetic and anti-obesity potential? Neuropeptides 2003, 37, 253-263.
33. Deacon, C. F. Therapeutic strategies based on glucagon-like peptide 1. Diabetes 2004, 53, 2181-2189.
34. Baggio, L. L.; Huang, Q.; Brown, T. J.; Drucker, D. J. A recombinant human glucagon-like peptide (GLP)-1-albumin protein (albugon) mimics peptidergic activation of GLP-1 receptor-dependent pathways coupled with satiety, gastrointestinal motility, and glucose homeostasis. Diabetes 2004, 53, 2492-2500.
35. Kim, J. G.; Baggio, L. L.; Bridon, D. P.; Castaigne, J. P.; Robitaille, M. F.; Jette, L.; Benquet, C.; Drucker, D. J. Development and characterisation of a glucagon-like peptide 1-albumin conjugate: the ability to activate the glucagon-like peptide 1 receptor in vivo. Diabetes 2003, 52, 751-759.
36. Göke, R.; Fehmann, H. C.; Linn, T.; Schmidt, H.; Krause, M.; Eng, J.; Göke, B. Exendin-4 is a high potency agonist and truncated exendin-(9-39)-amide an antagonist at the glucagon-like peptide 1-(7-36)-amide receptor of insulin-secreting beta-cells. J. Biol. Chem. 1993, 268, 19650-19655.
37. Meier, J. J.; Gallwitz, B.; Nauck, M. A. Glucagon-like peptide 1 and gastric inhibitory polypeptide: potential applications in type 2 diabetes mellitus. BioDrugs 2003, 17, 93-102.
38. Alana, I.; Hewage, C. M.; Malthouse, J. P.; Parker, J. C.; Gault, V. A.; O'Harte, F. P. M. NMR structure of the glucose-dependent insulinotropic polypeptide fragment, GIP(1-30)amide. Biochem. Biophys. Res. Commun. 2004, 325, 281-286.
39. Hinke, S. A.; Manhart, S.; Pamir, N.; Demuth, H.; Gelling, R.; Pederson, R. A.; McIntosh, C. H. Identification of a bioactive domain in the amino-terminus of glucose-dependent insulinotropic polypeptide (GIP). Biochim. Biophys. Acta. 2001, 1547, 143-155.
40. Kuhn-Wache, K.; Hoffmann, T.; Manhart, S.; Brandt, W.; Demuth, H. U. The specificity of DP IV for natural substrates is peptide structure determined. Adv. Exp. Med. Biol. 2003, 524, 57-63.
41. Bailey, C. J.; Flatt, P. R. Influence of genetic background and age on the expression of the obese hyperglycaemic syndrome in Aston ob/ob mice. Internat. J. Obes. 1982, 6, 11-21.
42. O'Harte, F. P. M.; Gray, A. M.; Flatt, P. R. Gastric inhibitory polypeptide and effects of glycation on glucose transport and metabolism in isolated mouse abdominal muscle. J. Endocrinol. 1998, 156, 237-243.
43. Hartmann, H.; Ebert, R.; Creutzfeldt, W. Insulin-dependent inhibition of hepatic glycogenolysis by gastric inhibitory polypeptide (GIP) in perfused rat liver. Diabetologia 1986, 29, 112-114.
44. Elahi, D.; Meneilly, G. S.; Minaker, K. L.; Rowe, J. W.; Anderson, D. K. Regulation of hepatic glucose uptake by gastric inhibitory polypeptide in man. Proceedings of Sixth International Conference on Gastrointestinal Hormones, Vancouver. 1986, p 18.
45. 13)GIP. Cell Biol. Internat. 2002, 27, 41-46.
46. Gremlich, S.; Porret, A.; Hani, E. H.; Cherif, D.; Vionnet, N.; Froguel, P.; Thorens, B. Cloning, functional expression, and chromosomal localisation of the human pancreatic islet glucose-dependent insulinotropic polypeptide receptor. Diabetes 1995, 44, 1202-1208.
47. McClenaghan, N. H.; Barnett, C. R.; Ah-Sing, E.; Abdel-Wahab, Y. H. A.; O'Harte, F. P. M.; Yoon, T.-W.; Swanston-Flatt, S. K.; Flatt, P. R. Characterization of a novel glucose-responsive insulin-secreting cell line, BRIN-BD11, produced by electrofusion. Diabetes 1996, 45, 1132-1140.
48. Stevens, J. F. Determination of glucose by an automatic analyser. Clin. Chem. Acta 1971, 32, 199-201.
49. Burington, R. S. Handbook of Mathematical Tables and Formulae; McGraw-Hill: New York, 1973.