Engineering a long-acting, potent GLP-1 analog for microstructure-based transdermal delivery

Proceedings of the National Academy of Sciences of the United States of America

Volumn 113, Issue 15, 2016, Pages 4140-4145

  Yang, Peng Yu ^a,b   Zou, Huafei ^b   Chao, Elizabeth ^b   Sherwood, Lance ^b   Nunez, Vanessa ^b   Keeney, Michael ^c   Ghartey Tagoe, Esi ^c   Ding, Zhongli ^c   Quirino, Herlinda ^b   Luo, Xiaozhou ^a   Welzel, Gus ^b   Chen, Guohua ^c   Singh, Parminder ^c   Woods, Ashley K ^b   Schultz, Peter G ^a,b   Shen, Weijun ^b  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b California Institute for Biomedical Research   (United States)

^c Corium International Inc ^*  (United States)

Author keywords

GLP 1 receptor agonist; Half life extension; Helix stabilization; Lipidated cross linker; Microstructure array

Indexed keywords

ANTIDIABETIC AGENT; CYCLIC AMP; EXENDIN 1; EXENDIN 4; EXENDIN 5; EXENDIN 6 PEPTIDE; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 1 RECEPTOR AGONIST; GLUCOSE; MESSENGER RNA; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIDIABETIC ACTIVITY; ARTICLE; COMPARATIVE STUDY; CONTROLLED STUDY; DIET INDUCED OBESITY; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG MEGADOSE; DRUG POTENCY; DRUG STRUCTURE; DUNKIN HARTLEY GUINEA PIG; ELIMINATION HALF-LIFE; FATTY LIVER; FEMALE; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLUCOSE TOLERANCE; IN VITRO STUDY; IN VIVO STUDY; LIPID METABOLISM; MALE; MAXIMUM PLASMA CONCENTRATION; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; ORAL GLUCOSE TOLERANCE TEST; PHARMACODYNAMICS; PLASMA HALF LIFE; PLASMA PROTEIN BINDING; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN ENGINEERING; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION; TRANSDERMAL PATCH; WEIGHT REDUCTION; AMINO ACID SEQUENCE; BIOSYNTHESIS; BODY WEIGHT; CHEMISTRY; CIRCULAR DICHROISM; CUTANEOUS DRUG ADMINISTRATION; GLUCOSE TOLERANCE TEST; HEK293 CELL LINE; HUMAN;

ADMINISTRATION, CUTANEOUS; AMINO ACID SEQUENCE; BODY WEIGHT; CIRCULAR DICHROISM; CYCLIC AMP; GLUCAGON-LIKE PEPTIDE 1; GLUCOSE TOLERANCE TEST; HEK293 CELLS; HUMANS; PROTEIN ENGINEERING;

EID: 84963579224     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1601653113     Document Type: Article

References (45)

1. Lagerström MC, Schiöth HB (2008) Structural diversity of G protein-coupled receptors and significance for drug discovery. Nat Rev Drug Discov 7(4):339-357.
2. Fosgerau K, Hoffmann T (2015) Peptide therapeutics: Current status and future directions. Drug Discov Today 20(1):122-128.
3. Jackson DY, King DS, Chmielewski J, Singh S, Schultz PG (1991) General approach to the synthesis of short alpha-helical peptides. J Am Chem Soc 113(24):9391-9392.
4. Leduc AM, et al. (2003) Helix-stabilized cyclic peptides as selective inhibitors of steroid receptor-coactivator interactions. Proc Natl Acad Sci USA 100(20):11273-11278.
5. Shepherd NE, Hoang HN, Abbenante G, Fairlie DP (2005) Single turn peptide alpha helices with exceptional stability in water. J Am Chem Soc 127(9):2974-2983.
6. Harrison RS, et al. (2010) Downsizing human, bacterial, and viral proteins to short water-stable alpha helices that maintain biological potency. Proc Natl Acad Sci USA 107(26):11686-11691.
7. Muppidi A, et al. (2012) Rational design of proteolytically stable, cell-permeable peptide-based selective Mcl-1 inhibitors. J Am Chem Soc 134(36):14734-14737.
8. Walensky LD, et al. (2004) Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix. Science 305(5689):1466-1470.
9. Chang YS, et al. (2013) Stapled α-helical peptide drug development: A potent dual inhibitor of MDM2 and MDMX for p53-dependent cancer therapy. Proc Natl Acad Sci USA 110(36):E3445-E3454.
10. Walensky LD, Bird GH (2014) Hydrocarbon-stapled peptides: Principles, practice, and progress. J Med Chem 57(15):6275-6288.
11. Chongsiriwatana NP, et al. (2008) Peptoids that mimic the structure, function, and mechanism of helical antimicrobial peptides. Proc Natl Acad Sci USA 105(8): 2794-2799.
12. Cheloha RW, Maeda A, Dean T, Gardella TJ, Gellman SH (2014) Backbone modification of a polypeptide drug alters duration of action in vivo. Nat Biotechnol 32(7): 653-655.
13. Johnson LM, et al. (2014) A potent α/β-peptide analogue of GLP-1 with prolonged action in vivo. J Am Chem Soc 136(37):12848-12851.
14. Havelund S, et al. (2004) The mechanism of protraction of insulin detemir, a longacting, acylated analog of human insulin. Pharm Res 21(8):1498-1504.
15. Drab SR, Philis-Tsimikas A (2014) A new option for glycemic control: Insulin degludec, a new-generation basal insulin with an ultralong duration of action. Pharmacotherapy 34(3):291-302.
16. Penchala SC, et al. (2015) A biomimetic approach for enhancing the in vivo half-life of peptides. Nat Chem Biol 11(10):793-798.
17. Harris JM, Chess RB (2003) Effect of pegylation on pharmaceuticals. Nat Rev Drug Discov 2(3):214-221.
18. Knop K, Hoogenboom R, Fischer D, Schubert US (2010) Poly(ethylene glycol) in drug delivery: Pros and cons as well as potential alternatives. Angew Chem Int Ed Engl 49(36):6288-6308.
19. Verhoef JJF, Anchordoquy TJ (2013) Questioning the use of PEGylation for drug delivery. Drug Deliv Transl Res 3(6):499-503.
20. Kopeček J (2013) Polymer-drug conjugates: Origins, progress to date and future directions. Adv Drug Deliv Rev 65(1):49-59.
21. Mitragotri S, Burke PA, Langer R (2014) Overcoming the challenges in administering biopharmaceuticals: Formulation and delivery strategies. Nat Rev Drug Discov 13(9): 655-672.
22. Schellenberger V, et al. (2009) A recombinant polypeptide extends the in vivo half-life of peptides and proteins in a tunable manner. Nat Biotechnol 27(12):1186-1190.
23. Ding S, et al. (2014) Multivalent antiviral XTEN-peptide conjugates with long in vivo half-life and enhanced solubility. Bioconjug Chem 25(7):1351-1359.
24. Jimenez-Solem E, Rasmussen MH, Christensen M, Knop FK (2010) Dulaglutide, a longacting GLP-1 analog fused with an Fc antibody fragment for the potential treatment of type 2 diabetes. Curr Opin Mol Ther 12(6):790-797.
25. Zhang Y, et al. (2015) Rational design of a humanized glucagon-like peptide-1 receptor agonist antibody. Angew Chem Int Ed Engl 54(7):2126-2130.
26. Liu T, et al. (2015) Functional human antibody CDR fusions as long-acting therapeutic endocrine agonists. Proc Natl Acad Sci USA 112(5):1356-1361.
27. Meier JJ (2012) GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol 8(12):728-742.
28. Donnelly D (2012) The structure and function of the glucagon-like peptide-1 receptor and its ligands. Br J Pharmacol 166(1):27-41.
29. Prausnitz MR, Langer R (2008) Transdermal drug delivery. Nat Biotechnol 26(11): 1261-1268.
30. Prausnitz MR (2004) Microneedles for transdermal drug delivery. Adv Drug Deliv Rev 56(5):581-587.
31. Sullivan SP, et al. (2010) Dissolving polymer microneedle patches for influenza vaccination. Nat Med 16(8):915-920.
32. Wendorf JR, et al. (2011) Transdermal delivery of macromolecules using solid-state biodegradable microstructures. Pharm Res 28(1):22-30.
33. Bonificio A, et al. (2015) Fabrication of cell culture-derived influenza vaccine dissolvable microstructures and evaluation of immunogenicity in guinea pigs. Vaccine 33(25):2930-2938.
34. Nielsen LL, Baron AD (2003) Pharmacology of exenatide (synthetic exendin-4) for the treatment of type 2 diabetes. Curr Opin Investig Drugs 4(4):401-405.
35. Muppidi A, et al. (2016) Design of potent and proteolytically stable oxyntomodulin analogs. ACS Chem Biol 11(2):324-328.
36. Runge S, Thøgersen H, Madsen K, Lau J, Rudolph R (2008) Crystal structure of the ligand-bound glucagon-like peptide-1 receptor extracellular domain. J Biol Chem 283(17):11340-11347.
37. Lyon RP, et al. (2014) Self-hydrolyzing maleimides improve the stability and pharmacological properties of antibody-drug conjugates. Nat Biotechnol 32(10):1059-1062.
38. Martínez-Palau M, Urpí L, Font-Bardia M, Puiggalí J (2005) N,N′-Butane-1,4-diylbis(bromoacetamide). Acta Crystallogr C 61(Pt 6):o345-o347.
39. Madsen K, et al. (2007) Structure-activity and protraction relationship of long-acting glucagon-like peptide-1 derivatives: Importance of fatty acid length, polarity, and bulkiness. J Med Chem 50(24):6126-6132.
40. Ward BP, et al. (2013) Peptide lipidation stabilizes structure to enhance biological function. Mol Metab 2(4):468-479.
41. Lau J, et al. (2015) Discovery of the once-weekly glucagon-like peptide-1 (GLP-1) analogue Semaglutide. J Med Chem 58(18):7370-7380.
42. Baggio LL, Drucker DJ (2014) Glucagon-like peptide-1 receptors in the brain: Controlling food intake and body weight. J Clin Invest 124(10):4223-4226.
43. Savage DB (2005) PPAR gamma as a metabolic regulator: Insights from genomics and pharmacology. Expert Rev Mol Med 7(1):1-16.
44. Eguchi Y, et al.; Japan Study Group for NAFLD (JSG-NAFLD) (2015) Pilot study of liraglutide effects in non-alcoholic steatohepatitis and non-alcoholic fatty liver disease with glucose intolerance in Japanese patients (LEAN-J). Hepatol Res 45(3):269-278.
45. Kenny PR, et al. (2010) Exenatide in the treatment of diabetic patients with nonalcoholic steatohepatitis: A case series. Am J Gastroenterol 105(12):2707-2709.