Design novel dual agonists for treating type-2 diabetes by targeting peroxisome proliferator-activated receptors with core hopping approach

PLoS ONE

Volumn 7, Issue 6, 2012, Pages

  Ma, Ying ^a   Wang, Shu Qing ^a,c   Xu, Wei Ren ^b   Wang, Run Ling ^a   Chou, Kuo Chen ^c  

^a TIANJIN MEDICAL UNIVERSITY   (China)

^b TIANJIN INSTITUTE OF PHARMACEUTICAL RESEARCH   (China)

^c GORDON LIFE SCIENCE INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIDIABETIC AGENT; GW 409544; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA AGONIST; TYROSINE DERIVATIVE; UNCLASSIFIED DRUG;

ANALYTIC METHOD; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; CORE HOPPING; DRUG CONFORMATION; DRUG DESIGN; DRUG RECEPTOR BINDING; DRUG RESEARCH; DRUG SCREENING; MOLECULAR DOCKING; MOLECULAR DYNAMICS; NON INSULIN DEPENDENT DIABETES MELLITUS; PROTEIN TARGETING;

BINDING SITES; DIABETES MELLITUS, TYPE 2; DRUG DESIGN; HUMANS; HYPOGLYCEMIC AGENTS; LIGANDS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; MOLECULAR DYNAMICS SIMULATION; MOLECULAR STRUCTURE; OXAZOLES; PPAR ALPHA; PPAR GAMMA; PROTEIN STRUCTURE, TERTIARY; TYROSINE;

EID: 84862004194     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0038546     Document Type: Article

References (78)

1. Lewis SN, Bassaganya-Riera J, Bevan DR, (2010) Virtual Screening as a Technique for PPAR Modulator Discovery. PPAR Res 2010: 861238.
2. Carpino PA, Goodwin B, (2010) Diabetes area participation analysis: a review of companies and targets described in the 2008-2010 patent literature. Expert Opin Ther Pat 20: 1627-1651.
3. Balakumar P, Rose M, Ganti SS, Krishan P, Singh M, (2007) PPAR dual agonists: are they opening Pandora's Box? Pharmacol Res 56: 91-98.
4. Markt P, Schuster D, Kirchmair J, Laggner C, Langer T, (2007) Pharmacophore modeling and parallel screening for PPAR ligands. J Comput Aided Mol Des 21: 575-590.
5. Shearer BG, Billin AN, (2007) The next generation of PPAR drugs: do we have the tools to find them? Biochim Biophys Acta 1771: 1082-1093.
6. Issemann I, Prince RA, Tugwood JD, Green S, (1993) The peroxisome proliferator-activated receptor:retinoid X receptor heterodimer is activated by fatty acids and fibrate hypolipidaemic drugs. J Mol Endocrinol 11: 37-47.
7. Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, et al. (1999) Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 341: 410-418.
8. Gangloff M, Ruff M, Eiler S, Duclaud S, Wurtz JM, et al. (2001) Crystal structure of a mutant hERalpha ligand-binding domain reveals key structural features for the mechanism of partial agonism. J Biol Chem 276: 15059-15065.
9. Rosen ED, Spiegelman BM, (2001) PPARgamma: a nuclear regulator of metabolism, differentiation, and cell growth. J Biol Chem 276: 37731-37734.
10. Blaschke F, Caglayan E, Hsueh WA, (2006) Peroxisome proliferator-activated receptor gamma agonists: their role as vasoprotective agents in diabetes. Endocrinol Metab Clin North Am 35: 561-574, ix.
11. Rubenstrunk A, Hanf R, Hum DW, Fruchart JC, Staels B, (2007) Safety issues and prospects for future generations of PPAR modulators. Biochim Biophys Acta 1771: 1065-1081.
12. Cronet P, Petersen JF, Folmer R, Blomberg N, Sjoblom K, et al. (2001) Structure of the PPARalpha and-gamma ligand binding domain in complex with AZ 242; ligand selectivity and agonist activation in the PPAR family. Structure 9: 699-706.
13. Mochizuki K, Suruga K, Yagi E, Takase S, Goda T, (2001) The expression of PPAR-associated genes is modulated through postnatal development of PPAR subtypes in the small intestine. Biochim Biophys Acta 1531: 68-76.
14. Chou KC, (2004) Review: Structural bioinformatics and its impact to biomedical science. Current Medicinal Chemistry 11: 2105-2134.
15. Chou KC, (2004) Molecular therapeutic target for type-2 diabetes. Journal of Proteome Research 3: 1284-1288.
16. Wang JF, Chou KC, (2011) Insights from modeling the 3D structure of New Delhi metallo-beta-lactamase and its binding interactions with antibiotic drugs. PLoS ONE 6: e18414.
17. Chou KC, Wei DQ, Zhong WZ, (2003) Binding mechanism of coronavirus main proteinase with ligands and its implication to drug design against SARS. (Erratum: Insights from modeling the 3D structure of New Delhi metallo-beta-lactamase and its binding interactions with antibiotic drugs, 2003, Vol.310, 675). Biochem Biophys Res Comm 308: 148-151.
18. Sirois S, Wei DQ, Du QS, Chou KC, (2004) Virtual Screening for SARS-CoV Protease Based on KZ7088 Pharmacophore Points. J Chem Inf Comput Sci 44: 1111-1122.
19. Dea-Ayuela MA, Perez-Castillo Y, Meneses-Marcel A, Ubeira FM, Bolas-Fernandez F, et al. (2008) HP-Lattice QSAR for dynein proteins: Experimental proteomics (2D-electrophoresis, mass spectrometry) and theoretic study of a Leishmania infantum sequence. Bioorg Med Chem 16: 7770-7776.
20. Prado-Prado FJ, de la Vega OM, Uriarte E, Ubeira FM, Chou KC, et al. (2009) Unified QSAR approach to antimicrobials. 4. Multi-target QSAR modeling and comparative multi-distance study of the giant components of antiviral drug-drug complex networks. Bioorg Med Chem: in press.
21. Prado-Prado FJ, Gonzalez-Diaz H, de la Vega OM, Ubeira FM, Chou KC, (2008) Unified QSAR approach to antimicrobials. Part 3: First multi-tasking QSAR model for Input-Coded prediction, structural back-projection, and complex networks clustering of antiprotozoal compounds. Bioorganic & Medicinal Chemistry 16: 5871-5880.
22. Prado-Prado FJ, Martinez de la Vega O, Uriarte E, Ubeira FM, Chou KC, et al. (2009) Unified QSAR approach to antimicrobials. 4. Multi-target QSAR modeling and comparative multi-distance study of the giant components of antiviral drug-drug complex networks. Bioorg Med Chem 17: 569-575.
23. Du QS, Huang RB, Wei YT, Pang ZW, Du LQ, et al. (2009) Fragment-Based Quantitative Structure-Activity Relationship (FB-QSAR) for Fragment-Based Drug Design. Journal of Computational Chemistry 30: 295-304.
24. Hou X, Du J, Fang H, Li M, (2011) 3D-QSAR Study on a Series of Bcl-2 Protein Inhibitors using Comparative Molecular Field Analysis. Protein and Peptide Letters 18: 440-449.
25. Xiao X, Wang P, Chou KC, (2011) GPCR-2L: Predicting G protein-coupled receptors and their types by hybridizing two different modes of pseudo amino acid compositions. Molecular Biosystems 7: 911-919.
26. Concu R, Dea-Ayuela MA, Perez-Montoto LG, Bolas-Fernandez F, Prado-Prado FJ, et al. (2009) Prediction of enzyme classes from 3D structure: a general model and examples of experimental-theoretic scoring of peptide mass fingerprints of Leishmania proteins. J Proteome Res 8: 4372-4382.
27. Chou KC, Wu ZC, Xiao X, (2011) iLoc-Euk: A Multi-Label Classifier for Predicting the Subcellular Localization of Singleplex and Multiplex Eukaryotic Proteins. PLoS One 6: e18258.
28. Chou KC, Wu ZC, Xiao X, (2012) iLoc-Hum: Using accumulation-label scale to predict subcellular locations of human proteins with both single and multiple sites. Molecular Biosystems 8: 629-641.
29. Wang P, Xiao X, Chou KC, (2011) NR-2L: A Two-Level Predictor for Identifying Nuclear Receptor Subfamilies Based on Sequence-Derived Features. PLoS ONE 6: e23505.
30. Xiao X, Wang P, Chou KC, (2012) iNR-PhysChem: A Sequence-Based Predictor for Identifying Nuclear Receptors and Their Subfamilies via Physical-Chemical Property Matrix. PLoS ONE 7: e30869.
31. Shen HB, Chou KC, (2008) HIVcleave: a web-server for predicting HIV protease cleavage sites in proteins. Analytical Biochemistry 375: 388-390.
32. Chou KC, (1993) A vectorized sequence-coupling model for predicting HIV protease cleavage sites in proteins. Journal of Biological Chemistry 268: 16938-16948.
33. Chou KC, (1996) Review: Prediction of HIV protease cleavage sites in proteins. Analytical Biochemistry 233: 1-14.
34. Schrodinger (2009) Core Hopping. Schrödinger, LLC, New York, NY, 2009.
35. Li XB, Wang SQ, Xu WR, Wang RL, Chou KC, (2011) Novel Inhibitor Design for Hemagglutinin against H1N1 Influenza Virus by Core Hopping Method. PLoS One 6: e28111.
36. CombiGlide2.5 (2009) Schrodinger LLC, New York, NY, 2009.
37. Xu HE, Lambert MH, Montana VG, Plunket KD, Moore LB, et al. (2001) Structural determinants of ligand binding selectivity between the peroxisome proliferator-activated receptors. Proc Natl Acad Sci U S A 98: 13919-13924.
38. Berman HM, Battistuz T, Bhat TN, Bluhm WF, Bourne PE, et al. (2002) The Protein Data Bank. Acta Crystallogr D Biol Crystallogr 58: 899-907.
39. Bowers KJ, Chow E, Xu H, Dror RO, Eastwood MP, et al. (2006) Scalable algorithms for molecular dynamics simulations on commodity clusters.
40. Prime2.1, Glide5.5 (2009) Schrodinger LLC, New York, NY, 2009.
41. Song Z, Kovacs FA, Wang J, Denny JK, Shekar SC, et al. (2000) Transmembrane domain of M2 protein from influenza A virus studied by solid-state (15)N polarization inversion spin exchange at magic angle NMR. Biophys J 79: 767-775.
42. Husslein T, Moore PB, Zhong Q, Newns DM, Pattnaik PC, et al. (1998) Molecular dynamics simulation of a hydrated diphytanol phosphatidylcholine lipid bilayer containing an alpha-helical bundle of four transmembrane domains of the influenza A virus M2 protein. Faraday Discuss: 201-208; discussion 225-246.
43. Kochendoerfer GG, Salom D, Lear JD, Wilk-Orescan R, Kent SB, et al. (1999) Total chemical synthesis of the integral membrane protein influenza A virus M2: role of its C-terminal domain in tetramer assembly. Biochemistry 38: 11905-11913.
44. Gandhi CS, Shuck K, Lear JD, Dieckmann GR, DeGrado WF, et al. (1999) Cu(II) inhibition of the proton translocation machinery of the influenza A virus M2 protein. J Biol Chem 274: 5474-5482.
45. Chou KC, Watenpaugh KD, Heinrikson RL, (1999) A Model of the complex between cyclin-dependent kinase 5 (Cdk5) and the activation domain of neuronal Cdk5 activator. Biochemical & Biophysical Research Communications 259: 420-428.
46. Zhang J, Luan CH, Chou KC, Johnson GVW, (2002) Identification of the N-terminal functional domains of Cdk5 by molecular truncation and computer modeling. PROTEINS: Structure, Function, and Genetics 48: 447-453.
47. Chou KC, (2004) Insights from modelling the 3D structure of the extracellular domain of alpha7 nicotinic acetylcholine receptor. Biochemical and Biophysical Research Communication 319: 433-438.
48. Housaindokht MR, Bozorgmehr MR, Bahrololoom M, (2008) Analysis of ligand binding to proteins using molecular dynamics simulations. J Theor Biol 254: 294-300.
49. Feige JN, Gelman L, Tudor C, Engelborghs Y, Wahli W, et al. (2005) Fluorescence imaging reveals the nuclear behavior of peroxisome proliferator-activated receptor/retinoid X receptor heterodimers in the absence and presence of ligand. J Biol Chem 280: 17880-17890.
50. Irwin JJ, Shoichet BK, (2005) ZINC-a free database of commercially available compounds for virtual screening. J Chem Inf Model 45: 177-182.
51. Liao QH, Gao QZ, Wei J, Chou KC, (2011) Docking and Molecular Dynamics Study on the Inhibitory Activity of Novel Inhibitors on Epidermal Growth Factor Receptor (EGFR). Medicinal Chemistry 7: 24-31.
52. Cai L, Wang Y, Wang JF, Chou KC, (2011) Identification of Proteins Interacting with Human SP110 During the Process of Viral Infections. Medicinal Chemistry 7: 121-126.
53. LigPre2.3 (2009) Schrodinger LLC, New York, NY, 2009.
54. Eldridge MD, Murray CW, Auton TR, Paolini GV, Mee RP, (1997) Empirical scoring functions: I. The development of a fast empirical scoring function to estimate the binding affinity of ligands in receptor complexes. J Comput Aided Mol Des 11: 425-445.
55. Halgren TA, Murphy RB, Friesner RA, Beard HS, Frye LL, et al. (2004) Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J Med Chem 47: 1750-1759.
56. Chou KC, (1984) The biological functions of low-frequency phonons: 3. Helical structures and microenvironment. Biophysical Journal 45: 881-890.
57. Wang JF, Chou KC, (2009) Insight into the molecular switch mechanism of human Rab5a from molecular dynamics simulations. Biochem Biophys Res Commun 390: 608-612.
58. Chou KC, (1989) Low-frequency resonance and cooperativity of hemoglobin. Trends in Biochemical Sciences 14: 212.
59. Chou KC, (1984) The biological functions of low-frequency phonons: 4. Resonance effects and allosteric transition. Biophysical Chemistry 20: 61-71.
60. Chou KC, (1987) The biological functions of low-frequency phonons: 6. A possible dynamic mechanism of allosteric transition in antibody molecules. Biopolymers 26: 285-295.
61. Chou KC, Mao B, (1988) Collective motion in DNA and its role in drug intercalation. Biopolymers 27: 1795-1815.
62. Chou KC, Zhang CT, Maggiora GM, (1994) Solitary wave dynamics as a mechanism for explaining the internal motion during microtubule growth. Biopolymers 34: 143-153.
63. Chou KC, (1988) Review: Low-frequency collective motion in biomacromolecules and its biological functions. Biophysical Chemistry 30: 3-48.
64. Javangula KC, Batchelor TJ, Jaber O, Watterson KG, Papagiannopoulos K, (2006) Combined severe pectus excavatum correction and aortic root replacement in Marfan's syndrome. Ann Thorac Surg 81: 1913-1915.
65. Kaminski GA, Friesner RA, Tirado-Rives J, Jorgensen WL, (2001) Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides. Journal of Physical Chemistry B 105: 6474-6487.
66. Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML, (1983) Comparison of simple potential functions for simulating liquid water. Journal of Chemical Physics 79: 926-935.
67. Hoover WG, (1985) Canonical dynamics: Equilibrium phase-space distributions. Phys Rev A 31: 1695-1697.
68. Jorgensen WL, Duffy EM, (2002) Prediction of drug solubility from structure. Adv Drug Deliv Rev 54: 355-366.
69. QikProp3.2 (2009) Schrodinger LLC, New York, NY, 2009.
70. Singh KD, Kirubakaran P, Nagarajan S, Sakkiah S, Muthusamy K, et al. (2011) Homology modeling, molecular dynamics, e-pharmacophore mapping and docking study of Chikungunya virus nsP2 protease. J Mol Model.
71. Ebdrup S, Pettersson I, Rasmussen HB, Deussen HJ, Frost Jensen A, et al. (2003) Synthesis and biological and structural characterization of the dual-acting peroxisome proliferator-activated receptor alpha/gamma agonist ragaglitazar. J Med Chem 46: 1306-1317.
72. Xu HE, Lambert MH, Montana VG, Parks DJ, Blanchard SG, et al. (1999) Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell 3: 397-403.
73. Michalik L, Zoete V, Krey G, Grosdidier A, Gelman L, et al. (2007) Combined simulation and mutagenesis analyses reveal the involvement of key residues for peroxisome proliferator-activated receptor alpha helix 12 dynamic behavior. J Biol Chem 282: 9666-9677.
74. Nolte RT, Wisely GB, Westin S, Cobb JE, Lambert MH, et al. (1998) Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma. Nature 395: 137-143.
75. Yue L, Ye F, Xu X, Shen J, Chen K, et al. (2005) The conserved residue Phe273(282) of PPARalpha(gamma), beyond the ligand-binding site, functions in binding affinity through solvation effect. Biochimie 87: 539-550.
76. Ji CG, Zhang JZ, (2008) Protein polarization is critical to stabilizing AF-2 and helix-2′ domains in ligand binding to PPAR-gamma. J Am Chem Soc 130: 17129-17133.
77. Liu XY, Wang SQ, Xu WR, Tang LD, Wang RL, et al. (2011) Docking and Molecular Dynamics Simulations of Peroxisome Proliferator Activated Receptors Interacting with Pan Agonist Sodelglitazar. Protein Pept Lett.
78. Liu G, Xin Z, Pei Z, Hajduk PJ, Abad-Zapatero C, et al. (2003) Fragment screening and assembly: a highly efficient approach to a selective and cell active protein tyrosine phosphatase 1B inhibitor. J Med Chem 46: 4232-4235.