Discovery of a novel small molecule inhibitor targeting the frataxin/ubiquitin interaction via structure-based virtual screening and bioassays

Journal of Medicinal Chemistry

Volumn 56, Issue 7, 2013, Pages 2861-2873

  Lavecchia, Antonio ^a   Di Giovanni, Carmen ^a   Cerchia, Carmen ^a   Russo, Annapina ^a   Russo, Giulia ^a   Novellino, Ettore ^a  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

6 [(2,3 DIMETHOXYPHENYL)(4 MORPHOLINYL)METHYL] 1,3 BENZODIOXOL 5 OL; BENZYLOXYCARBONYLLEUCYLLEUCYLLEUCINAL; BORTEZOMIB; FRATAXIN; NSC 137976; NSC 151852; NSC 172191; NSC 194314; NSC 349165; NSC 363043; NSC 379644; NSC 381576; NSC 403389; NSC 405602; NSC 72530; NSC 74981; NSC 96398; PROTEASOME; UBIQUITIN; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; BINDING ASSAY; CONTROLLED STUDY; DRUG BINDING SITE; DRUG IDENTIFICATION; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG SCREENING; DRUG SYNTHESIS; DRUG TARGETING; FRIEDREICH ATAXIA; HUMAN; HUMAN CELL; LIGAND BINDING; MOLECULAR DOCKING; MOLECULAR LIBRARY; MOLECULAR MODEL; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; UBIQUITINATION; VIRTUAL REALITY;

BIOLOGICAL ASSAY; BLOTTING, WESTERN; CHROMATOGRAPHY, LIQUID; DRUG DISCOVERY; HEK293 CELLS; HUMANS; IRON-BINDING PROTEINS; MASS SPECTROMETRY; MODELS, MOLECULAR; SMALL MOLECULE LIBRARIES; STRUCTURE-ACTIVITY RELATIONSHIP; UBIQUITIN;

EID: 84876243806     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm3017199     Document Type: Article

References (53)

1. Harding, A. E. Classification of the hereditary ataxias and paraplegias Lancet 1983, 1, 1151-1155
2. Campuzano, V.; Montermini, L.; Molto, M. D.; Pianese, L.; Cossee, M.; Cavalcanti, F.; Monros, E.; Rodius, F.; Duclos, F.; Monticelli, A.; Zara, F.; Canizares, J.; Koutnikova, H.; Bidichandani, S. I.; Gellera, C.; Brice, A.; Trouillas, P.; De Michele, G.; Filla, A.; De Frutos, R.; Palau, F.; Patel, P. I.; Di Donato, S.; Mandel, J. L.; Cocozza, S.; Koenig, M.; Pandolfo, M. Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion Science 1996, 271, 1423-1427
3. Delatycki, M. B.; Williamson, R.; Forrest, S. M. Friedreich ataxia: an overview J. Med. Genet. 2000, 37, 1-8
4. Pandolfo, M. Friedreich ataxia: detection of GAA repeat expansions and frataxin point mutations Methods Mol. Med. 2006, 126, 197-216
5. Patel, P. I.; Isaya, G. Friedreich ataxia: from GAA triplet-repeat expansion to frataxin deficiency Am. J. Hum. Genet. 2001, 69, 15-24
6. Harding, A. E. Friedreich's ataxia: a clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features Brain 1981, 104, 589-620
7. Harding, A. E. Clinical features and classification of inherited ataxias Adv. Neurol. 1993, 61, 1-14
8. De Michele, G.; Filla, A.; Cavalcanti, F.; Di Maio, L.; Pianese, L.; Castaldo, I.; Calabrese, O.; Monticelli, A.; Varrone, S.; Campanella, G.; Leone, M.; Pandolfo, M.; Cocozza, S. Late onset Friedreich's disease: clinical features and mapping of mutation to the FRDA locus J. Neurol., Neurosurg. Psychiatry 1994, 57, 977-979
9. Sakamoto, N.; Ohshima, K.; Montermini, L.; Pandolfo, M.; Wells, R. D. Sticky DNA, a self-associated complex formed at long GAA*TTC repeats in intron 1 of the frataxin gene, inhibits transcription J. Biol. Chem. 2001, 276, 27171-27177
10. Pandolfo, M. Frataxin deficiency and mitochondrial dysfunction Mitochondrion 2002, 2, 87-93
11. Pandolfo, M. Friedreich Ataxia and Related RNA Loss-of-Function Disorders. In Molecular Neurology, 1 st ed.; Waxman, S., Ed.; Elsevier Academic Press: San Diego, CA, 2007; pp 277-294.
12. CondoÌ, I.; Ventura, N.; Malisan, F.; Rufini, A.; Tomassini, B.; Testi, R. In vivo maturation of human frataxin Hum. Mol. Genet. 2007, 16, 1534-1540
13. Schmucker, S.; Argentini, M.; Carelle-Calmels, N.; Martelli, A.; Puccio, H. The in vivo mitochondrial two-step maturation of human frataxin Hum. Mol. Genet. 2008, 17, 3521-3531
14. Cavadini, P.; Adamec, J.; Taroni, F.; Gakh, O.; Isaya, G. Two-step processing of human frataxin by mitochondrial processing peptidase. Precursor and intermediate forms are cleaved at different rates J. Biol. Chem. 2000, 275, 41469-41475
15. Koutnikova, H.; Campuzano, V.; Koenig, M. Maturation of wild-type and mutated frataxin by the mitochondrial processing peptidase Hum. Mol. Genet. 1998, 7, 1485-1489
16. Acquaviva, F.; De Biase, I.; Nezi, L.; Ruggiero, G.; Tatangelo, F.; Pisano, C.; Monticelli, A.; Garbi, C.; Acquaviva, A. M.; Cocozza, S. Extra-mitochondrial localisation of frataxin and its association with IscU1 during enterocyte-like differentiation of the human colon adenocarcinoma cell line Caco-2 J. Cell Sci. 2005, 118, 3917-3924
17. CondoÌ, I.; Ventura, N.; Malisan, F.; Tomassini, B.; Testi, R. A pool of extramitochondrial frataxin that promotes cell survival J. Biol. Chem. 2006, 281, 16750-16756
18. Lu, C.; Cortopassi, G. Frataxin knockdown causes loss of cytoplasmic iron-sulfur cluster functions, redox alterations and induction of heme transcripts Arch. Biochem. Biophys. 2007, 457, 111-122
19. CondoÌ, I.; Malisan, F.; Guccini, I.; Serio, D.; Rufini, A.; Testi, R. Molecular control of the cytosolic aconitase/IRP1 switch by extramitochondrial frataxin Hum. Mol. Genet. 2010, 19, 1221-1229
20. Rufini, A.; Fortuni, S.; Arcuri, G.; CondoÌ, I.; Serio, D.; Incani, O.; Malisan, F.; Ventura, N.; Testi, R. Preventing the ubiquitin-proteasome-dependent degradation of frataxin, the protein defective in Friedreich's ataxia Hum. Mol. Genet. 2011, 20, 1253-1261
21. Dominguez, C.; Boelens, R.; Bonvin, A. HADDOCK: a protein-protein docking approach based on biochemical or biophysical information J. Am. Chem. Soc. 2003, 125, 1731-1737
22. 15N-relaxation data Proteins 2005, 60, 367-381
23. Dhe-Paganon, S.; Shigeta, R.; Chi, Y. I.; Ristow, M.; Shoelson, S. E. Crystal structure of human frataxin J. Biol. Chem. 2000, 275, 30753-30756
24. Vijay-Kumar, S.; Bugg, C. E.; Cook, W. J. Structure of ubiquitin refined at 1.8 Å resolution J. Mol. Biol. 1987, 194, 531-544
25. de Vries, S. J.; van Dijk, A. D. J.; Bonvin, A. M. WHISCY: What information does surface conservation yield? Application to data-driven docking Proteins 2006, 63, 479-489
26. Neuvirth, H.; Raz, R.; Schreiber, G. ProMate: a structure based prediction program to identify the location of protein-protein binding sites J. Mol. Biol. 2004, 338, 181-199
27. Swanson, K. A.; Kang, R. S.; Stamenova, S. D.; Hicke, L.; Radhakrishnan, I. Solution structure of Vps27 UIM-ubiquitin complex important for endosomal sorting and receptor downregulation EMBO J. 2003, 22, 4597-4606
28. Lee, S.; Tsai, Y. C.; Mattera, R.; Smith, W. J.; Kostelansky, M. S.; Weissman, A. M.; Bonifacino, J. S.; Hurley, J. H. Structural basis for ubiquitin recognition and autoubiquitination by Rabex-5 Nat. Struct. Mol. Biol. 2006, 13, 264-271
29. Schmucker, S.; Martelli, A.; Colin, F.; Page, A.; Wattenhofer- Donzé, M.; Reutenauer, L.; Puccio, H. Mammalian frataxin: an essential function for cellular viability through an interaction with a preformed ISCU/NFS1/ISD11 iron-sulfur assembly complex PLoS One 2011, 6, e16199
30. Leidgens, S.; De Smet, S.; Foury, F. Frataxin interacts with Isu1 through a conserved tryptophan in its β-sheet Hum. Mol. Genet. 2010, 19, 276-286
31. Shan, Y.; Napoli, E.; Cortopassi, G. A. Mitochondrial frataxin interacts with ISD11 of the NFS1/ISCU complex and multiple mitochondrial chaperones Hum. Mol. Genet. 2007, 16, 929-941
32. Tsai, C. L.; Bridwell-Rabb, J.; Barondeau, D. P. Friedreich's ataxia variants I154F and W155R diminish frataxin-based activation of the iron-sulfur cluster assembly complex Biochemistry 2011, 50, 6478-6487
33. Developmental Therapeutics Program, National Cancer Institute. http://dtp.cancer.gov/.
34. Charifson, P. S.; Walters, W. P. Filtering databases and chemical libraries J. Comput.-Aided Mol. Des. 2002, 16, 311-323
35. Oprea, T. I.; Bologa, C.; Olah, M.; Alvarez, J.; Shoichet, B. Compound Selection for Virtual Screening. In Virtual Screening in Drug Discovery, Eds.; Taylor & Francis: Boca Raton, FL, 2005; pp 89-106.
36. FILTER, version 2.0.1; OpenEye Scientific Software Inc.: Santa Fe, NM; http://www.eyesopen.com (accessed Sep 2009).
37. GLIDE, version 5.7; Schrodinger, LLC: New York, 2011; http://www.schrodinger.com/.
38. Morris, G. M.; Goodsell, D. S.; Halliday, R. S.; Huey, R.; Hart, W. E.; Belew, R. K.; Olson, A. J. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function J. Comput. Chem. 1998, 19, 1639-1662
39. Jacques, J.; Collet, A.; Wilen, S. H. Enantiomers, Racemates, and Resolutions; Wiley: New York, 1981.
40. Nikolic, D.; Habibi-Goudarzi, S.; Corley, D. G.; Gafner, S.; Pezzuto, J. M.; Van Breemen, R. B. Evaluation of cyclooxygenase-2 inhibitors using pulsed ultrafiltration mass spectrometry Anal. Chem. 2000, 72, 3853-3859
41. Liu, D.; Guo, J.; Luo, Y.; Broderick, D. J.; Schimerlik, M. I.; Pezzuto, J. M.; Breemen, R. B. Screening for ligands of human retinoid X receptor-alpha using ultrafiltration mass spectrometry Anal. Chem. 2007, 79, 9398-9402
42. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The Protein Data Bank Nucleic Acids Res. 2000, 28, 235-242
43. Sander, C.; Schneider, R. Database of homology-derived protein structures and the structural meaning of sequence alignment Proteins 1991, 9, 56-68
44. Linge, J. P.; Williams, M. A.; Spronk, C. A.; Bonvin, A. M.; Nilges, M. Refinement of protein structures in explicit solvent Proteins 2003, 50, 496-506
45. Jorgensen, W. L.; Tirado-Rives, J. The OPLS potential function for proteins. Energy minimization for crystals of cyclic peptides and crambin J. Am. Chem. Soc. 1998, 110, 1657-1666
46. McDonald, I. K.; Thornton, J. M. Satisfying hydrogen bonding potential in proteins J. Mol. Biol. 1994, 238, 777-793
47. Irwin, J. J.; Shoichet, B. K. ZINC-a free database of commercially available compounds for virtual screening J. Chem. Inf. Model. 2005, 45, 177-182
48. Charifson, P. S.; Corkery, J. J.; Murcko, M. A.; Walters, W. P. Consensus scoring: a method for obtaining improved hit rates from docking databases of three-dimensional structures into proteins J. Med. Chem. 1999, 42, 5100-5109
49. Oda, A.; Tsuchida, K.; Takakura, T.; Yamaotsu, N.; Hirono, S. Comparison of consensus scoring strategies for evaluating computational models of protein-ligand complexes J. Chem. Inf. Model. 2006, 46, 380-391
50. QikProp, version 3.4; Schrödinger LLC: New York, 2011.
51. Ihlenfeldt, W. D.; Voigt, J. H.; Bienfait, B.; Oellien, F.; Nicklaus, M. C. Enhanced CACTVS browser of the open NCI database J. Chem. Inf. Comput. Sci. 2002, 42, 46-57
52. Willett, P. Similarity-based approaches to virtual screening Biochem. Soc. Trans. 2003, 31, 603-606
53. Martin, Y. C.; Kofron, J. L.; Traphagen, L. M. Do structurally similar molecules have similar biological activity? J. Med. Chem. 2002, 45, 4350-4358