On the origin of the stereoselective affinity of Nutlin-3 geometrical isomers for the MDM2 protein

Cell Cycle

Volumn 12, Issue 24, 2013, Pages 3727-3735

  ElSawy, Karim M ^a,b   Verma, Chandra S ^c,d,e   Lane, David P ^f   Caves, Leo S D ^a  

^a UNIVERSITY OF YORK   (United Kingdom)

^b QASSIM UNIVERSITY   (Saudi Arabia)

^c BIOINFORMATICS INSTITUTE   (Singapore)

^d NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^e NANYANG TECHNOLOGICAL UNIVERSITY   (Singapore)

^f AGENCY FOR SCIENCE   (Singapore)

Author keywords

Brownian dynamics simulation; Encounter complex; Kinetics based drug discovery; MDM2 protein; Nutlin stereoselectivity; Residence time; Stereoselectivity

Indexed keywords

ARGININE; GLUTAMIC ACID; LYSINE; NUTLIN 3; PROTEIN MDM2; PROTEIN P53;

ARTICLE; BINDING AFFINITY; BINDING SITE; BROWNIAN DYNAMIC SIMULATION; DIASTEREOISOMER; ELECTRIC POTENTIAL; ENANTIOMER; ISOMER; MOLECULAR DYNAMICS; PROTEIN ANALYSIS; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; PROTEIN STABILITY; PROTEIN STRUCTURE; STEREOCHEMISTRY;

BROWNIAN DYNAMICS SIMULATION; ENCOUNTER COMPLEX; KINETICS-BASED DRUG DISCOVERY; MDM2 PROTEIN; NUTLIN STEREOSELECTIVITY; RESIDENCE TIME; STEREOSELECTIVITY;

ANTINEOPLASTIC AGENTS; BINDING SITES; IMIDAZOLES; MOLECULAR DYNAMICS SIMULATION; MUTATION; PIPERAZINES; PROTEIN BINDING; PROTO-ONCOGENE PROTEINS C-MDM2; STEREOISOMERISM;

EID: 84891858447     PISSN: 15384101     EISSN: 15514005     Source Type: Journal    
DOI: 10.4161/cc.27273     Document Type: Article

References (65)

1. Goodsell DS, Olson AJ. Structural symmetry and protein function. Annu Rev Biophys Biomol Struct 2000; 29:105-53; PMID:10940245; http://dx.doi.org/10. 1146/annurev.biophys.29.1.105
2. Avetisov V, Goldanskii V. Mirror symmetry breaking at the molecular level. Proc Natl Acad Sci U S A 1996; 93:11435-42; PMID:8876153; http://dx.doi.org/10.1073/pnas.93.21.11435
3. Goodman G, Gershwin ME. The origin of life and the left-handed amino-acid excess: the furthest heavens and the deepest seas? Exp Biol Med (Maywood) 2006; 231:1587-92; PMID:17060678
4. Jorissen A, Cerf C. Asymmetric photoreactions as the origin of biomolecular homochirality: a critical review. Orig Life Evol Biosph 2002; 32:129-42; PMID:12185672; http://dx.doi.org/10.1023/A:1016087202273
5. Hill SA. Correct nomenclature for stereo isomers. Anaesthesia 2002; 57:200; PMID:11871988; http://dx.doi.org/10.1046/j.1365-2044.2002.2470-30.x
6. Cahn RS, Ingold C, Prelog V. Specification of Molecular Chirality. Angew Chem Int Ed Engl 1966; 5:385-415; http://dx.doi.org/10.1002/anie.196603851
7. Hirschmann H, Hanson KR. The differentiation of stereoheterotopic groups. Eur J Biochem 1971; 22:301-9; PMID:5125353; http://dx.doi.org/10.1111/j.1432- 1033.1971.tb01545.x
8. Orr-Ewing AJ. Dynamical stereochemistry of bimolecular reactions. J Chem Soc, Faraday Trans 1996; 92:881-900; http://dx.doi.org/10.1039/ft9969200881
9. Kim YK, Arai MA, Arai T, Lamenzo JO, Dean EF 3rd, Patterson N, Clemons PA, Schreiber SL. Relationship of stereochemical and skeletal diversity of small molecules to cellular measurement space. J Am Chem Soc 2004; 126:14740-5; PMID:15535697; http://dx.doi.org/10.1021/ja048170p
10. Islam MR, Mahdi JG, Bowen ID. Pharmacological importance of stereochemical resolution of enantiomeric drugs. Drug Saf 1997; 17:149-65; PMID:9306051; http://dx.doi.org/10.2165/00002018-199717030-00002
11. Hutt AJ. The development of single-isomer molecules: why and how. CNS Spectr 2002; 7(Suppl 1):14-22; PMID:15131488
12. Nguyen LA, He H, Pham-Huy C. Chiral drugs: an overview. Int J Biomed Sci 2006; 2:85-100; PMID:23674971
13. McConathy J, Owens MJ. Stereochemistry in Drug Action. Prim Care Companion J Clin Psychiatry 2003; 5:70-3; PMID:15156233; http://dx.doi.org/10. 4088/PCC.v05n0202
14. Cotzias GC, Van Woert MH, Schiffer LM. Aromatic amino acids and modification of parkinsonism. N Engl J Med 1967; 276:374-9; PMID:5334614; http://dx.doi.org/10.1056/NEJM196702162760703
15. Cotzias GC, Papavasiliou PS, Gellene R. Modification of Parkinsonism - chronic treatment with L-dopa. N Engl J Med 1969; 280:337-45; PMID:4178641; http://dx.doi.org/10.1056/NEJM196902132800701
16. Brown CJ, Cheok CF, Verma CS, Lane DP. Reactivation of p53: from peptides to small molecules. Trends Pharmacol Sci 2011; 32:53-62; PMID:21145600; http://dx.doi.org/10.1016/j.tips.2010.11.004
17. Vassilev LT. MDM2 inhibitors for cancer therapy. Trends Mol Med 2007; 13:23-31; PMID:17126603; http://dx.doi.org/10.1016/j.molmed.2006.11.002
18. Verma R, Rigatti MJ, Belinsky GS, Godman CA, Giardina C. DNA damage response to the Mdm2 inhibitor nutlin-3. Biochem Pharmacol 2010; 79:565-74; PMID:19788889; http://dx.doi.org/10.1016/j.bcp.2009.09.020
19. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004; 303:844-8; PMID:14704432; http://dx.doi.org/10.1126/science.1092472
20. Secchiero P, Bosco R, Celeghini C, Zauli G. Recent advances in the therapeutic perspectives of Nutlin-3. Curr Pharm Des 2011; 17:569-77; PMID:21391907; http://dx.doi.org/10.2174/138161211795222586
21. Kojima K, Konopleva M, Samudio IJ, Shikami M, Cabreira-Hansen M, McQueen T, Ruvolo V, Tsao T, Zeng Z, Vassilev LT, et al. MDM2 antagonists induce p53-dependent apoptosis in AML: implications for leukemia therapy. Blood 2005; 106:3150-9; PMID:16014563; http://dx.doi.org/10.1182/blood-2005-02-0553
22. Sharma V, Peddibhotla S, Tepe JJ. Sensitization of cancer cells to DNA damaging agents by imidazolines. J Am Chem Soc 2006; 128:9137-43; PMID:16834387; http://dx.doi.org/10.1021/ja060273f
23. Srivastava S, Beck B, Wang W, Czarna A, Holak TA, Dömling A. Rapid and efficient hydrophilicity tuning of p53/mdm2 antagonists. J Comb Chem 2009; 11:631-9; PMID:19548636; http://dx.doi.org/10.1021/cc9000218
24. Czarna A, Beck B, Srivastava S, Popowicz GM, Wolf S, Huang Y, Bista M, Holak TA, Dömling A. Robust generation of lead compounds for protein-protein interactions by computational and MCR chemistry: p53/Hdm2 antagonists. Angew Chem Int Ed Engl 2010; 49:5352-6; PMID:20575124; http://dx.doi.org/10.1002/anie.201001343
25. Anil B, Riedinger C, Endicott JA, Noble ME. The structure of an MDM2-Nutlin-3a complex solved by the use of a validated MDM2 surface-entropy reduction mutant. Acta Crystallogr D Biol Crystallogr 2013; 69:1358-66; PMID:23897459; http://dx.doi.org/10.1107/S0907444913004459
26. Fry DC, Emerson SD, Palme S, Vu BT, Liu CM, Podlaski F. NMR structure of a complex between MDM2 and a small molecule inhibitor. J Biomol NMR 2004; 30:163-73; PMID:15557803; http://dx.doi.org/10.1023/B:JNMR.0000048856.84603.9b
27. Fischer PM. Peptide, Peptidomimetic, and Small-molecule Antagonists of the p53-HDM2 Protein-Protein Interaction. Int J Pept Res Ther 2006; 12:3-19; PMID:19617922; http://dx.doi.org/10.1007/s10989-006-9016-5
28. Davis TA, Johnston JN. Catalytic, Enantioselective Synthesis of Stilbene cis-Diamines: A Concise Preparation of (-)-Nutlin-3, a Potent p53/MDM2 Inhibitor. Chem Sci 2011; 2:1076-9; PMID:22708054; http://dx.doi.org/10.1039/ c1sc00061f
29. Joseph TL, Madhumalar A, Brown CJ, Lane DP, Verma CS. Differential binding of p53 and nutlin to MDM2 and MDMX: computational studies. Cell Cycle 2010; 9:1167-81; PMID:20190571; http://dx.doi.org/10.4161/cc.9.6.11067
30. ElSawy KM, Verma CS, Joseph TL, Lane DP, Twarock R, Caves LS. On the interaction mechanisms of a p53 peptide and nutlin with the MDM2 and MDMX proteins: a Brownian dynamics study. Cell Cycle 2013; 12:394-404; PMID:23324352; http://dx.doi.org/10.4161/cc.23511
31. Dastidar SG, Lane DP, Verma CS. Modulation of p53 binding to MDM2: computational studies reveal important roles of Tyr100. BMC Bioinformatics 2009; 10(Suppl 15):S6; PMID:19958516; http://dx.doi.org/10.1186/1471-2105-10-S15-S6
32. Burke D, Henderson DJ. Chirality: a blueprint for the future. Br J Anaesth 2002; 88:563-76; PMID:12066734; http://dx.doi.org/10.1093/bja/88.4.563
33. Brooks WH, Guida WC, Daniel KG. The significance of chirality in drug design and development. Curr Top Med Chem 2011; 11:760-70; PMID:21291399; http://dx.doi.org/10.2174/156802611795165098
34. Ogston AG. Interpretation of experiments on metabolic processes, using isotopic tracer elements. Nature 1948; 162:963; PMID:18225319; http://dx.doi.org/10.1038/162963b0
35. Mesecar AD, Koshland DE Jr. A new model for protein stereospecificity. Nature 2000; 403:614-5; PMID:10688187
36. Henrich S, Salo-Ahen OM, Huang B, Rippmann FF, Cruciani G, Wade RC. Computational approaches to identifying and characterizing protein binding sites for ligand design. J Mol Recognit 2010; 23:209-19; PMID:19746440
37. Lu H, Tonge PJ. Drug-target residence time: critical information for lead optimization. Curr Opin Chem Biol 2010; 14:467-74; PMID:20663707; http://dx.doi.org/10.1016/j.cbpa.2010.06.176
38. Swinney DC. The role of binding kinetics in therapeutically useful drug action. Curr Opin Drug Discov Devel 2009; 12:31-9; PMID:19152211
39. Copeland RA, Pompliano DL, Meek TD. Drug-target residence time and its implications for lead optimization. Nat Rev Drug Discov 2006; 5:730-9; PMID:16888652; http://dx.doi.org/10.1038/nrd2082
40. Tummino PJ, Copeland RA. Residence time of receptor-ligand complexes and its effect on biological function. Biochemistry 2008; 47:5481-92; PMID:18412369; http://dx.doi.org/10.1021/bi8002023
41. Copeland RA. The dynamics of drug-target interactions: drug-target residence time and its impact on efficacy and safety. Expert Opin Drug Discov 2010; 5:305-10; PMID:22823083; http://dx.doi.org/10.1517/17460441003677725
42. Yun C-H, Mengwasser KE, Toms AV, Woo MS, Greulich H, Wong K-K, Meyerson M, Eck MJ. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci U S A 2008; 105:2070-5; PMID:18227510; http://dx.doi.org/10.1073/pnas.0709662105
43. Petty TJ, Emamzadah S, Costantino L, Petkova I, Stavridi ES, Saven JG, Vauthey E, Halazonetis TD. An induced fit mechanism regulates p53 DNA binding kinetics to confer sequence specificity. EMBO J 2011; 30:2167-76; PMID:21522129; http://dx.doi.org/10.1038/emboj.2011.127
44. Swinney DC. Applications of Binding Kinetics to Drug Discovery: Translation of Binding Mechanisms to Clinically Differentiated Therapeutic Responses. Pharmaceutical Medicine 2008; 22:23-34; http://dx.doi.org/10.1007/ BF03256679
45. Zhang R, Monsma F. The importance of drug-target residence time. Curr Opin Drug Discov Devel 2009; 12:488-96; PMID:19562645
46. ElSawy KM, Twarock R, Lane DP, Verma CS, Caves LSD. Characterization of the Ligand Receptor Encounter Complex and Its Potential for in Silico Kinetics-Based Drug Development. J Chem Theory Comput 2012; 8:314-21; http://dx.doi.org/10.1021/ct200560w
47. Gabdoulline RR, Wade RC. On the protein-protein diffusional encounter complex. J Mol Recognit 1999; 12:226-34; PMID:10440993; http://dx.doi.org/10. 1002/(SICI)1099-1352(199907/08)12:4〈226::AID-JMR462〉3.0.CO;2-P
48. Tang C, Iwahara J, Clore GM. Visualization of transient encounter complexes in protein-protein association. Nature 2006; 444:383-6; PMID:17051159; http://dx.doi.org/10.1038/nature05201
49. Suh JY, Tang C, Clore GM. Role of electrostatic interactions in transient encounter complexes in protein-protein association investigated by paramagnetic relaxation enhancement. J Am Chem Soc 2007; 129:12954-5; PMID:17918946; http://dx.doi.org/10.1021/ja0760978
50. Edelstein SJ, Stefan MI, Le Novère N. Ligand depletion in vivo modulates the dynamic range and cooperativity of signal transduction. PLoS One 2010; 5:e8449; PMID:20052284; http://dx.doi.org/10.1371/journal.pone.0008449
51. Brooks BR, Brooks CL 3rd, Mackerell AD Jr., Nilsson L, Petrella RJ, Roux B, Won Y, Archontis G, Bartels C, Boresch S, et al. CHARMM: the biomolecular simulation program. J Comput Chem 2009; 30:1545-614; PMID:19444816; http://dx.doi.org/10.1002/jcc.21287
52. Caves LSD, Evanseck JD, Karplus M. Locally accessible conformations of proteins: multiple molecular dynamics simulations of crambin. Protein Sci 1998; 7:649-66; PMID:9541397; http://dx.doi.org/10.1002/pro.5560070314
53. Elsawy KM, Hodgson MK, Caves LSD. The physical determinants of the DNA conformational landscape: an analysis of the potential energy surface of single-strand dinucleotides in the conformational space of duplex DNA. Nucleic Acids Res 2005; 33:5749-62; PMID:16214808; http://dx.doi.org/10.1093/nar/gki888
54. Gabdoulline RR, Wade RC. Simulation of the diffusional association of barnase and barstar. Biophys J 1997; 72:1917-29; PMID:9129797; http://dx.doi.org/10.1016/S0006-3495(97)78838-6
55. Gabdoulline RR, Wade RC. Brownian dynamics simulation of protein-protein diffusional encounter. Methods 1998; 14:329-41; PMID:9571088; http://dx.doi.org/10.1006/meth.1998.0588
56. Donald LE, McCammon JA. Brownian dynamics with hydrodynamic interactions. J Chem Phys 1978; 69:1352-60; http://dx.doi.org/10.1063/1.436761
57. García De La Torre J, Huertas ML, Carrasco B. Calculation of hydrodynamic properties of globular proteins from their atomic-level structure. Biophys J 2000; 78:719-30; PMID:10653785; http://dx.doi.org/10.1016/S0006- 3495(00)76630-6
58. Im W, Beglov D, Roux B. Continuum Solvation Model: computation of electrostatic forces from numerical solutions to the Poisson-Boltzmann equation. Comput Phys Commun 1998; 111:59-75; http://dx.doi.org/10.1016/S0010-4655(98) 00016-2
59. Coalson R, Beck TL. Numerical Methods for Solving Poisson and Poisson-Boltzmann Type Equations. In: von Rague Schleyer P, ed. Encyclopedia of Computational Chemistry. New York: John-Wiley, 1998:2086-100.
60. Baker NA, Sept D, Joseph S, Holst MJ, McCammon JA. Electrostatics of nanosystems: application to microtubules and the ribosome. Proc Natl Acad Sci U S A 2001; 98:10037-41; PMID:11517324; http://dx.doi.org/10.1073/pnas.181342398
61. Dolinsky TJ, Czodrowski P, Li H, Nielsen JE, Jensen JH, Klebe G, Baker NA. PDB2PQR: expanding and upgrading automated preparation of biomolecular structures for molecular simulations. Nucleic Acids Res 2007; 35:W522-5; PMID:17488841; http://dx.doi.org/10.1093/nar/gkm276
62. Czodrowski P, Dramburg I, Sotriffer CA, Klebe G. Development, validation, and application of adapted PEOE charges to estimate pKa values of functional groups in protein-ligand complexes. Proteins: Struct, Funct. Bioinf 2006; 65:424-37
63. Gabdoulline RR, Wade RC. Protein-protein association: investigation of factors influencing association rates by brownian dynamics simulations. J Mol Biol 2001; 306:1139-55; PMID:11237623; http://dx.doi.org/10.1006/jmbi.2000.4404
64. Elcock AH, Gabdoulline RR, Wade RC, McCammon JA. Computer simulation of protein-protein association kinetics: acetylcholinesterase-fasciculin. J Mol Biol 1999; 291:149-62; PMID:10438612; http://dx.doi.org/10.1006/jmbi.1999.2919
65. Gabdoulline RR, Wade RC. Effective Charges for Macromolecules in Solvent. J Phys Chem 1996; 100:3868-78; http://dx.doi.org/10.1021/jp953109f