Synthesis, pharmacological evaluation, and molecular modeling studies of novel peptidic CAAX analogues as farnesyl-protein-transferase inhibitors

Journal of Medicinal Chemistry

Volumn 49, Issue 6, 2006, Pages 1882-1890

  Santagada, Vincenzo ^a   Caliendo, Giuseppe ^a   Severino, Beatrice ^a   Lavecchia, Antonio ^a   Perissutti, Elisa ^a   Fiorino, Ferdinando ^a   Zampella, Angela ^b   Sepe, Valentina ^b   Califano, Daniela ^c   Santelli, Giovanni ^c   Novellino, Ettore ^a  

^a Dipartimento di Chimica Farmaceutica e Tossicologica   (Italy)

^b UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^c NATIONAL CANCER INSTITUTE   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

AROMATIC COMPOUND; ESTER DERIVATIVE; FARNESYL TRANS TRANSFERASE; METHYL GROUP; PEPTIDE DERIVATIVE; PHENYLALANINE; PROTEIN FARNESYLTRANSFERASE INHIBITOR; PSEUDOPEPTIDE; TYROSINE;

AMINO ACID SUBSTITUTION; ANIMAL CELL; ARTICLE; CARBOXY TERMINAL SEQUENCE; CELL TRANSFORMATION; DIASTEREOISOMER; DRUG BINDING SITE; DRUG CYTOTOXICITY; DRUG POTENCY; DRUG SCREENING; DRUG SELECTIVITY; DRUG SYNTHESIS; ENZYME INHIBITION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; IC 50; MOLECULAR MODEL; MOUSE; NONHUMAN; PROTEIN MOTIF; RAT; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION;

ALANINE; ALKYL AND ARYL TRANSFERASES; ANIMALS; BINDING SITES; CELL LINE; CELL LINE, TUMOR; HUMANS; INDOLES; MICE; MODELS, MOLECULAR; OLIGOPEPTIDES; RATS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; TYROSINE;

EID: 33645393448     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0506165     Document Type: Article

References (29)

1. Reid, S. T.; Beese L. S. Crystal structures of the anticancer clinical candidates R115777 (Tipifarnib) and BMS-214662 complexed with protein farnesyltransferase suggest a mechanism of FTI selectivity. Biochemistry, 2004, 43, 6877-6884.
2. El Oualid, F.; Burm, B. E. A.; Leroy, I. M.; Cohen, L. H.; van Boom, J. H.; van den Elst, H.; Overkleeft, H. S.; van der Marel, G. A.; Overhand, M. Design, synthesis, and evaluation of sugar amino acid based inhibitors of protein prenyl transferases PFT and PGGT-1. J. Med. Chem. 2004, 47, 3920-3923.
3. Brunner, T. B.; Hahn, S. M.; Gupta, A. K.; Muschel, R. J.; McKenna, W. G.; Bernhard, E. J. Farnesyltransferase inhibitors: an overview of the results of preclinical and clinical investigations. Cancer Res. 2003, 63, 5656-5668.
4. Long, S. B.; Hancock, P. J.; Kral, A. M.; Hellinga, H. W.; Beese, L. S. The crystal structure of human protein farnesyltransferase reveals the structural basis for inhibition by CaaX tetrapeptides and their mimetics. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 12948-12953.
5. Bell, I. M. Inhibitors of farnesyltransferase: a rational approach to cancer chemotherapy? J. Med. Chem. 2004, 47, 1869-1878.
6. 2X motif. Bioorg. Med. Chem. Lett. 1994, 4, 887-892.
7. Lee, H. Y.; Sohn, J. H.; Kwon, B. M. Development of tripeptidyl farnesyltransferase inhibitors. Bioorg. Med. Chem. Lett. 2002, 12, 1599-1602.
8. (a) Caliendo, G.; Fiorino, F.; Grieco, P.; Perissutti, E.; Santagada, V.; Ramunno, A.; Albrizio, S.; Califano, D.; Giuliano, A.; Santelli, G. Phenol-derived CVFM analog inhibitors of Ras Famesyltransferase possessing cellular in vitro activity Eur. J. Med. Chem. 1998, 33, 725-732.
9. (b) Caliendo, G.; Fiorino, F.; Grieco, P.; Perissutti, E.; De Luca, S.; Giuliano, A.; Santelli, G.; Califano, D.; Severino, B.; Santagada, V. Synthesis and biological activity of pseudopeptides inhibitors of Ras farnesyl transferase containing unconventional amino acids. Farmaco. 1999, 54, 785-790.
10. Santagada, V.; Caliendo, G.; Severino, B.; Perissutti, E.; Ceccarelli, F.; Giusti, L.; Mazzoni, M. R.; Salvadori, S.; Temussi, P. A. Probing the shape of a hydrophobic pocket in the active site of delta-opioid antagonists. J. Pept. Sci. 2001, 7, 374-385.
11. (a) Vincent, M.; Remond, G.; Portevin, B.; Serkiz, B.; Laubie, M. Stereoselective synthesis of a new perhydroindole derivative of chiral iminodiacid, a potent inhibitor of angiotensin converting enzyme. Tetrahedron Lett. 1982, 23, 1677-1680.
12. Sheehan, J. C.; Yang, D. D. H. The use of N-formylamino acids in peptide synthesis. J. Am. Chem. Soc. 1958, 80, 1154-1158.
13. (a) Harada, K.; Fujii, K.; Mayumi, T.; Hibino, Y.; Suzuki, M. A method using LC/MS for determination of absolute configuration of constituent amino acids in peptide advanced Marfey's method. Tetrahedron Lett. 1995, 36, 1515-1518.
14. (b) Fujii, K.; Ikai, Y.; Mayumi, T.; Oka, H.; Suzuki, M.; Harada, K. A nonempirical method using LC/MS for determination of the absolute configuration of constituent amino acids in a peptide: elucidation of limitations of Marfey's method and of its separation mechanism. Anal. Chem. 1997, 69, 3346-3352.
15. Péter, A.; Olajos, E.; Casimir, R.; Tourwé. D.; Broxterman, Q. B.; Kaptein, B.; Armstrong, D. W. High-performance liquid Chromatographic separation of the enantiomers of unusual amino acid analogues. J. Chromatogr., A 2000, 871, 105-113.
16. Davidson, I. Protein Sequencing Protocol. In Methods in Molecular Biology. 2nd ed.; Smith, B. J., Ed.; Humana Press: Totowa, NJ,; Vol. 211.
17. (a) Smith, V.; Rowlands, M. G.; Barrie, E.; Workman, P.: Kelland, L. R. Establishment and characterization of acquired resistance to the farnesyl protein transferase inhibitor R115777 in a human colon cancer cell line. Clin. Cancer Res. 2002, 8, 2002-2009.
18. (b) Moasser, M. M.; Rosen, N. The use of molecular markers in farnesyltransferase inhibitor (FTI) therapy of breast cancer. Breast Cancer Res. Treat. 2002, 73, 135-144.
19. (a) Strickland, C. L.; Windsor, W. T.; Syto, R.; Wang, L.; Bond, R.; Wu, R.; Schwartz, J.; Le, H. V.; Beese, L. S.; Weber, P. C. Crystal structure of farnesyl protein transferase complexed with a CaaX peptide and farnesyl diphosphate analogue. Biochemistry 1998, 37, 16601-16611.
20. (b) Long, S. B.; Casey, P. J.; Beese, L. S. The basis for K-Ras4B binding specificity to protein farnesyltransferase revealed by 2 Å resolution ternary complex structures. Structure 2000, 8, 209-222.
21. Desiraju, G. R.; Steiner, T. Monographs on Crystallography: Oxford University Press/International Union of Crystallography: Oxford, 1999: Vol, 9.
22. Reiss, Y.; Stradley, S. J.; Gierasch, L. M.; Brown, M. S.; Goldstein, J. L. Sequence requirement for peptide recognition by rat brain p21Ras protein farnesyltransferase. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 732-736.
23. Hightower, K. E.; Huang, C.-C.; Casey, P. J.; Fierke, C. A. H-Ras peptide and protein substrates bind protein farnesyltransferase as an ionized thiolate. Biochemistry, 1999, 37, 15555-15562.
24. SYBYL Molecular Modeling System. version 6.9.1; Tripos Inc.: St. Louis, MO, 2003.
25. Head, J.; Zerner, M. C. A Broyden-Fletcher-Goldfarb-Shannon optimization procedure for molecular geometries. Chem. Phys. Lett. 1985, 122, 264-274.
26. Vinter, J. G.; Davis, A.; Saunders, M. R. Strategic Approaches to Drug Design. 1. An integrated software framework for molecular modeling. J. Comput.-Aided Mol. Des. 1987, 1, 31-55.
27. Reiss, Y.; Goldstein, J. L.; Seabra, M. C.; Casey, P. J.; Brown, M. S. Inhibition of purified p21Ras farnesyl protein transferase by Cys-AAX tetrapeptides. Cell 1990, 62, 81-88.
28. Fusco, A.; Berlingieri, M. T.; Di Fiore, P. P.; Portella, G.; Grieco, M.; Vecchio, G. One- and two-step transformations of rat thyroid epithelial cells by retroviral oncogenes. Mol. Cell. Biol. 1987, 7, 3365-3370.
29. Skehan, P.; Storeng, R.; Scudiero, D.; Monks, A.; McMahon, J.; Vistica, D.; Warren, J. T.; Bokesch, H.; Kenney, S.; Boyd, M. R. New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst. 1990, 82, 1107-1112.