Biopolym. Cell. 2013; 29(4):339-347.
http://dx.doi.org/10.7124/bc.000828
Огляди
Раціональний дизайн інгібіторів протеїнкіназ
1Ярмолюк С. М., 1Нипорко О. Ю., 1Бджола В. Г.
  1. Інститут молекулярної біології і генетики НАН України
    Вул. Академіка Заболотного, 150, Київ, Україна, 03680

Abstract

Сучасні методологічні підходи до раціонального дизайну низькомолекулярних сполук, що характеризуються специфічною активністю щодо заданих біомолекулярних мішеней, розглянуто на прикладі розробки високоефективних інгібіторів протеїнкіназ. Висвітлено нові обчислювальні методи, застосування яких дає змогу суттєво покращити якість комп’ютерних експериментів (зокрема, точність передбачення активності низькомолекулярних сполук) без збільшення розрахункових потужностей та витрати часу. Ефективність стратегії раціонального дизайну підтверджено низкою власних досліджень з розробки нових інгібіторів протеїнкіназ СК2, FGFR1 і ASK1.
Keywords: раціональний дизайн, інгібітори протеїнкіназ, низькомолекулярні сполуки, протеїнкінази СК2, FGFR1, ASK1
Повний текст: (PDF, англійською)

References

[1] Manning G., Whyte D. B., Martinez R., Hunter T., Sudarsanam S. The protein kinase complement of the human genome Science 2002 298, N 5600:1912–1934.
[2] Johnson L. N., Noble M. E., Owen D. J. Active and inactive protein kinases: structural basis for regulation Cell 1996 85, N 2:149–158.
[3] Huse M., Kuriyan J. The conformational plasticity of protein kinases Cell 2002 109, N 3:275–282.
[4] Nolen B., Taylor S., Ghosh G. Regulation of protein kinases; controlling activity through activation segment conformation Mol. Cell 2004 15, N 5:661–675.
[5] Blume-Jensen P., Hunter T. Oncogenic kinase signalling Nature 2001 411, N 6835:355–365.
[6] Murray N. R., Kalari K. R., Fields A. P. Protein kinase Ci expression and oncogenic signaling mechanisms in cancer J. Cell. Physiol 2011 226, N 4:879–887.
[7] Cohen P. Protein kinases – the major drug targets of the twentyfirst century? Nat. Rev. Drug Discov 2002 1, N 4:309–315.
[8] Petrelli A., Giordano S. From singleto multi-target drugs in cancer therapy: when aspecificity becomes an advantage Curr. Med. Chem 2008 15, N 5:422–432.
[9] Backes A. C., Zech B., Felber B., Klebl B., Muller G. Small-molecule inhibitors binding to protein kinases. Part I: exceptions from the traditional pharmacophore approach of type I inhibition Expert Opin. Drug Discov 2008 3, N 12:1409–1425.
[10] Schwartz P. A., Murray B. W. Protein kinase biochemistry and drug discovery Bioorg. Chem 2011 39, N 5–6:192–210.
[11] Eglen R., Reisine T. Drug discovery and the human kinome: recent trends Pharmacol. Ther 2011 130, N 2:144–156.
[12] Yakovenko O., Oliferenko A. A., Bdzhola V. G., Palyulin V. A., Zefirov N. S. Kirchhoff atomic charges fitted to multipole moments: Implementation for a virtual screening system J. Comput. Chem 2008 29, N 8:1332–1343.
[13] Yakovenko O. Y., Li Y. Y., Oliferenko A. A. et al. Ab initio parameterization of YFF1, a universal force field for drug-design applications J. Mol. Model 2012 18, N 2:663–673.
[14] Yakovenko O. Ya., Oliferenko A. A., Golub G. A., Bdzhla V. G., Yarmolyuk S. M. The new method of distribution integrals evaluations for high throughput virtual screening Ukr. Bioorg. Acta 2007 5, N 1:52–62.
[15] Oliferenko A. A., Palyulin V. A., Pisarev S. A., Neiman A. V., Zefirov N. S. Novel point charge models: reliable instruments for molecular electrostatic J. Phys. Org. Chem 2001 14, N 6 P. 355–369.
[16] Halgren T. A. Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94 J. Comp. Chem 1996 17, N 5–6:490–519.
[17] Ooi T., Oobatake M., Nemethy G., Scheraga H. A. Accessible surface-areas as a measure of the thermodynamic properties of hydration of peptides Proc. Natl Acad. Sci. USA 1987 84, N 10:3086–3090.
[18] Bruccoleri R. E., Novotny J., Davis M. E. Finite difference Poisson-Boltzmann electrostatic calculations: increased accuracy achieved by harmonic dielectric smoothing and charge antialiasing J. Comput. Chem 1997 18, N 2:268–276.
[19] Hawkins G. D., Cramer C. J., Truhlar D. G. Pairwise solute descreening of solute charges from a dielectric medium Chem. Phys. Lett 1995 246, N 1–2:122–129.
[20] Yakovenko O. Ya., Golub A. G., Bdzhola V. G., Yarmoluk S. M. Application of distribution function of rotation and translation degrees of freedom for CK2 inhibitors Ki estimation Ukr. Bioorg. Acta 2006 4, N 2:47–55.
[21] Dittie A. S., Thomas L., Thomas G., Tooze S. A. Interaction of furin in immature secretory granules from neuroendocrine cells with the AP-1 adaptor complex is modulated by casein kinase II phosphorylation EMBO J 1997 16, N 16:4859–4870.
[22] Mauxion F., Le Borgne R., Munier-Lehmann H., Hoflack B. A casein kinase II phosphorylation site in the cytoplasmic domain of the cation-dependent mannose 6-phosphate receptor determines the high affinity interaction of the AP-1 Golgi assembly proteins with membranes J. Biol. Chem 1997 271, N 4 P. 2171–2178.
[23] Sarrouilhe D., Filhol O., Leroy D. et al. The tight association of protein kinase CK2 with plasma membrane is mediated by a specific domain of its regulatory beta-subunit Biochim. Biophys. Acta 1998 1403, N 2:199–210.
[24] Faust M., Montenarh M. Subcellular localization of protein kinase CK2. A key to its function? Cell Tissue Res 2000 301, N 3:329–340.
[25] Meggio F., Pinna L. A. One-thousand-and-one substrates of protein kinaseCK2? FASEB J 2003 17, N 3:349–368.
[26] Ahmad K. A., Wang G., Unger G., Slaton J., Ahmed K. Protein kinase CK2 – a key suppressor of apoptosis Adv. Enzyme Regul 2008 48:179–187.
[27] Filhol O., Cochet C. Protein kinase CK2 in health and disease: cellular functions of protein kinase CK2: a dynamic affair Cell. Mol. Life Sci 2009 66, N 11–12:1830–1839.
[28] St-Denis N. A., Litchfield D. W. Protein kinase CK2 in health and disease: from birth to death: the role of protein kinase CK2 in the regulation of cell proliferation and survival Cell. Mol. Life Sci 2009 66, N 11–12:1817–1829.
[29] Daya-Makin M., Sanghera J. S., Morgentale T. L. et al. Activation of a tumor-ssociated protein kinase (p40TAK) and casein kinase 2 in human squamous cell carcinomas and adenocarcinomas of the lung Cancer Res 1994 54, N 8:2262– 2268.
[30] Faust R. A., Gapany M., Tristani P. et al. Elevated protein kinase CK2 activity in chromatin of head and neck tumors: association with malignant transformation Cancer Lett 1996 101, N 1:31–35.
[31] Landesman-Bollag E., Romieu-Mourez R., Song D. H. et al. Protein kinase CK2 in mammary gland tumorigenesis Oncogene 2001 20, N 25:3247–3257.
[32] Stalter G., Siemer S., Becht E. et al. Asymmetric expression of protein kinase CK2 subunits in human kidney tumors Biochem. Biophys. Res. Commun 1994 202, N 1:141–147.
[33] Trembley J. H., Wang G., Unger G., Slaton J., Ahmed K. Protein kinase CK2 in health and disease: CK2: a key player in cancer biology Cell. Mol. Life Sci 2009 66, N 11–12 P. 1858–1867.
[34] Yenice S., Davis A. T., Goueli S. A. et al. Nuclear casein kinase 2 (CK-2) activity in human normal, benign hyperplastic, and cancerous prostate Prostate 1994 24, N 1–P. 11–16.
[35] Raftery M., Campbell R., Glaros E. N., et al. Phosphorylation of apolipoproteinE at an atypical protein kinase CK2 PSD/E site in vitro Biochemistry 2005 44, N 19:7346–7353.
[36] Yamada M., Katsuma S., Adachi T. et al. Inhibition of protein kinase CK2 prevents the progression of glomerulonefritis Proc. Natl Acad. Sci. USA 2005 102, N 21:7736–7741.
[37] Singh N. N., Ramji D. P. Protein kinase CK2, an important regulator of the inflammatory response? J. Mol. Med. (Berl) 2008 86, N 8:887–897.
[38] Ljubimov A. V., Caballero S., Aoki A. M. et al. Involvement of protein kinase CK2 in angiogenesis and retinal neovascularization Invest. Ophthalmol. Vis. Sci 2004 45, N 12:4583–4591.
[39] Cozza G., Pinna L. A., Moro S. Protein kinase CK2 inhibitors: a patent review Expert Opin. Ther. Patents 2012 22, N 9:1081–1097.
[40] Pat. UA68984 A, C07D215/00. Application of 4-substituted 3-carboxyquinolines as protein kinase CK2 inhibitors / V. M. Sapelkin, S. S. Lukashov, A. G. Golub, O. Ya. Yakovenko, V. G. Bdzhola, G. G.Dubinina, S.M. Yarmoluk Publ. 2004-08-16.
[41] Golub A. G., Yakovenko O. Y., Bdzhola V. G. et al. Evaluation of 3-carboxy-4(1H)-quinolones as inhibitors of human protein kinase CK2 J. Med. Chem 2006 49, N 22:6443–6450.
[42] Pat. UA69165 A, C07D215/00. Application of 4,5,6,7-tetrahalogeno-1,3-isoindolinediones as protein kinase CK2 inhibitors / A. O. Prykhod’ko, A. G. Golub, O. Ya. Yakovenko, V. G. Bdzhola, G. G. Dubinina, S. M. Yarmoluk Publ. 2004-08-16.
[43] Golub A. G., Yakovenko O. Y., Prykhod'ko A. O., et al. Evaluation of 4,5,6,7-tetrahalogeno-1H-isoindole-1,3(2H)-diones as inhibitors of human protein kinase CK2 Biochim. Biophys. Acta 2008 1784, N 1:143–149.
[44] Battistutta R., De Moliner E., Sarno S., Zanotti G., Pinna L. A. Structural features underlying selective inhibition of protein kinase CK2 by ATP-site directed tetrabromo-2-benzotriazole Protein Sci 2001 10, N 11:2200–2206.