The multi-leu peptide inhibitor discriminates between PACE4 and furin and exhibits antiproliferative effects on prostate cancer cells

Journal of Medicinal Chemistry

Volumn 55, Issue 23, 2012, Pages 10501-10511

  Levesque, Christine ^a   Fugère, Martin ^a,d   Kwiatkowska, Anna ^a   Couture, Frédéric ^a   Desjardins, Roxane ^a   Routhier, Sophie ^a   Moussette, Philippe ^a   Prahl, Adam ^b   Lammek, Bernard ^b   Appel, Jon R ^c   Houghten, Richard A ^c   D'Anjou, François ^a   Dory, Yves L ^a   Neugebauer, Witold ^a   Day, Robert ^a  

^a UNIVERSITÉ DE SHERBROOKE   (Canada)

^b UNIVERSITY OF GDA SK   (Poland)

^c TORREY PINES INSTITUTE FOR MOLECULAR STUDIES   (United States)

^d SALK INSTITUTE FOR BIOLOGICAL STUDIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FURIN; LEUCYLLEUCYLLEUCYLLEUCYLARGINYLVALYLLYSYLARGININE; PROTEIN PACE4; SERINE PROTEINASE; SERINE PROTEINASE INHIBITOR; UNCLASSIFIED DRUG;

ANTIPROLIFERATIVE ACTIVITY; ARTICLE; CANCER CELL; CONTROLLED STUDY; G1 PHASE CELL CYCLE CHECKPOINT; HUMAN; HUMAN CELL; PROSTATE CANCER; PROTEIN FOLDING;

AMINO ACID SEQUENCE; CELL LINE, TUMOR; FURIN; HUMANS; MALE; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; OLIGOPEPTIDES; PROPROTEIN CONVERTASES; PROSTATIC NEOPLASMS; RECOMBINANT PROTEINS; SEQUENCE HOMOLOGY, AMINO ACID; SERINE ENDOPEPTIDASES;

EID: 84870985285     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm3011178     Document Type: Article

References (41)

1. Fugere, M.; Day, R. Cutting back on pro-protein convertases: the latest approaches to pharmacological inhibition Trends Pharmacol. Sci. 2005, 26 (6) 294-301
2. Couture, F.; D'Anjou, F.; Day, R. On the cutting edge of proprotein convertase pharmacology: from molecular concepts to clinical applications Biomol. Concepts 2011, 2 (5) 421-438
3. D'Anjou, F.; Routhier, S.; Perreault, J. P.; Latil, A.; Bonnel, D.; Fournier, I.; Salzet, M.; Day, R. Molecular Validation of PACE4 as a Target in Prostate Cancer Transl. Oncol. 2011, 4 (3) 157-172
4. Seidah, N. G.; Mayer, G.; Zaid, A.; Rousselet, E.; Nassoury, N.; Poirier, S.; Essalmani, R.; Prat, A. The activation and physiological functions of the proprotein convertases Int. J. Biochem. Cell Biol. 2008, 40 (6-7) 1111-1125
5. Mayer, G.; Hamelin, J.; Asselin, M. C.; Pasquato, A.; Marcinkiewicz, E.; Tang, M.; Tabibzadeh, S.; Seidah, N. G. The regulated cell surface zymogen activation of the proprotein convertase PC5A directs the processing of its secretory substrates J. Biol. Chem. 2008, 283 (4) 2373-2384
6. Nour, N.; Mayer, G.; Mort, J. S.; Salvas, A.; Mbikay, M.; Morrison, C. J.; Overall, C. M.; Seidah, N. G. The cysteine-rich domain of the secreted proprotein convertases PC5A and PACE4 functions as a cell surface anchor and interacts with tissue inhibitors of metalloproteinases Mol. Biol. Cell 2005, 16 (11) 5215-5226
7. Klee, E. W.; Bondar, O. P.; Goodmanson, M. K.; Dyer, R. B.; Erdogan, S.; Bergstralh, E. J.; Bergen, H. R., III; Sebo, T. J.; Klee, G. G. Candidate Serum Biomarkers for Prostate Adenocarcinoma Identified by mRNA Differences in Prostate Tissue and Verified with Protein Measurements in Tissue and Blood Clin. Chem. 2012, 58, 599-609
8. Henrich, S.; Lindberg, I.; Bode, W.; Than, M. E. Proprotein convertase models based on the crystal structures of furin and kexin: explanation of their specificity J. Mol. Biol. 2005, 345 (2) 211-227
9. Tian, S.; Jianhua, W. Comparative study of the binding pockets of mammalian proprotein convertases and its implications for the design of specific small molecule inhibitors Int. J. Biol. Sci. 2010, 6 (1) 89-95
10. Lindberg, I.; van den Hurk, W. H.; Bui, C.; Batie, C. J. Enzymatic characterization of immunopurified prohormone convertase 2: potent inhibition by a 7B2 peptide fragment Biochemistry 1995, 34 (16) 5486-5493
11. van Horssen, A. M.; van den Hurk, W. H.; Bailyes, E. M.; Hutton, J. C.; Martens, G. J.; Lindberg, I. Identification of the region within the neuroendocrine polypeptide 7B2 responsible for the inhibition of prohormone convertase PC2 J. Biol. Chem. 1995, 270 (24) 14292-14296
12. Basak, A.; Lazure, C. Synthetic peptides derived from the prosegments of proprotein convertase 1/3 and furin are potent inhibitors of both enzymes Biochem. J. 2003, 373 (Pt 1) 231-239
13. Fugere, M.; Limperis, P. C.; Beaulieu-Audy, V.; Gagnon, F.; Lavigne, P.; Klarskov, K.; Leduc, R.; Day, R. Inhibitory potency and specificity of subtilase-like pro-protein convertase (SPC) prodomains J. Biol. Chem. 2002, 277 (10) 7648-7656
14. Zhong, M.; Munzer, J. S.; Basak, A.; Benjannet, S.; Mowla, S. J.; Decroly, E.; Chretien, M.; Seidah, N. G. The prosegments of furin and PC7 as potent inhibitors of proprotein convertases. In vitro and ex vivo assessment of their efficacy and selectivity J. Biol. Chem. 1999, 274 (48) 33913-33920
15. Cameron, A.; Appel, J.; Houghten, R. A.; Lindberg, I. Polyarginines are potent furin inhibitors J. Biol. Chem. 2000, 275 (47) 36741-36749
16. Kacprzak, M. M.; Peinado, J. R.; Than, M. E.; Appel, J.; Henrich, S.; Lipkind, G.; Houghten, R. A.; Bode, W.; Lindberg, I. Inhibition of furin by polyarginine-containing peptides: nanomolar inhibition by nona- d -arginine J. Biol. Chem. 2004, 279 (35) 36788-36794
17. Roebroek, A. J.; Umans, L.; Pauli, I. G.; Robertson, E. J.; van Leuven, F.; van de Ven, W. J.; Constam, D. B. Failure of ventral closure and axial rotation in embryos lacking the proprotein convertase Furin Development 1998, 125 (24) 4863-4876
18. Kim, W.; Essalmani, R.; Szumska, D.; Creemers, J. W.; Roebroek, A. J.; D'Orleans-Juste, P.; Bhattacharya, S.; Seidah, N. G.; Prat, A. Loss of endothelial furin leads to cardiac malformation and early postnatal death Mol. Cell. Biol. 2012, 32, 3382-3391
19. Nakayama, K. Furin: a mammalian subtilisin/Kex2p-like endoprotease involved in processing of a wide variety of precursor proteins Biochem. J. 1997, 327 (Pt 3) 625-635
20. Anderson, E. D.; VanSlyke, J. K.; Thulin, C. D.; Jean, F.; Thomas, G. Activation of the furin endoprotease is a multiple-step process: requirements for acidification and internal propeptide cleavage EMBO J. 1997, 16 (7) 1508-1518
21. Krysan, D. J.; Rockwell, N. C.; Fuller, R. S. Quantitative characterization of furin specificity. Energetics of substrate discrimination using an internally consistent set of hexapeptidyl methylcoumarinamides J. Biol. Chem. 1999, 274 (33) 23229-23234
22. Molloy, S. S.; Anderson, E. D.; Jean, F.; Thomas, G. Bi-cycling the furin pathway: from TGN localization to pathogen activation and embryogenesis Trends Cell Biol. 1999, 9 (1) 28-35
23. Houghten, R. A.; Pinilla, C.; Appel, J. R.; Blondelle, S. E.; Dooley, C. T.; Eichler, J.; Nefzi, A.; Ostresh, J. M. Mixture-based synthetic combinatorial libraries J. Med. Chem. 1999, 42 (19) 3743-3778
24. Houghten, R. A.; Wilson, D. B.; Pinilla, C. Drug discovery and vaccine development using mixture-based synthetic combinatorial libraries Drug Discovery Today 2000, 5 (7) 276-285
25. Eichler, J. Synthetic peptide arrays and peptide combinatorial libraries for the exploration of protein-ligand interactions and the design of protein inhibitors Comb. Chem. High Throughput Screening 2005, 8 (2) 135-143
26. Apletalina, E.; Appel, J.; Lamango, N. S.; Houghten, R. A.; Lindberg, I. Identification of inhibitors of prohormone convertases 1 and 2 using a peptide combinatorial library J. Biol. Chem. 1998, 273 (41) 26589-26595
27. Fugere, M.; Appel, J.; Houghten, R. A.; Lindberg, I.; Day, R. Short polybasic peptide sequences are potent inhibitors of PC5/6 and PC7: use of positional scanning-synthetic peptide combinatorial libraries as a tool for the optimization of inhibitory sequences Mol. Pharmacol. 2007, 71 (1) 323-332
28. Seidah, N. G.; Prat, A. The biology and therapeutic targeting of the proprotein convertases Nature Rev. Drug Discovery 2012, 11 (5) 367-383
29. Creemers, J. W.; Khatib, A. M. Knock-out mouse models of proprotein convertases: unique functions or redundancy? Front. Biosci. 2008, 13, 4960-4971
30. Seidah, N. G.; Chretien, M.; Day, R. The family of subtilisin/kexin like pro-protein and pro-hormone convertases: divergent or shared functions Biochimie 1994, 76 (3-4) 197-209
31. Henrich, S.; Cameron, A.; Bourenkov, G. P.; Kiefersauer, R.; Huber, R.; Lindberg, I.; Bode, W.; Than, M. E. The crystal structure of the proprotein processing proteinase furin explains its stringent specificity Nature Struct. Biol. 2003, 10 (7) 520-526
32. Voorhorst, W. G.; Warner, A.; de Vos, W. M.; Siezen, R. J. Homology modelling of two subtilisin-like proteases from the hyperthermophilic archaea Pyrococcus furiosus and Thermococcus stetteri Protein Eng. 1997, 10 (8) 905-914
33. Piper, D. E.; Jackson, S.; Liu, Q.; Romanow, W. G.; Shetterly, S.; Thibault, S. T.; Shan, B.; Walker, N. P. The crystal structure of PCSK9: a regulator of plasma LDL-cholesterol Structure 2007, 15 (5) 545-552
34. Krowarsch, D.; Cierpicki, T.; Jelen, F.; Otlewski, J. Canonical protein inhibitors of serine proteases Cell. Mol. Life Sci. 2003, 60 (11) 2427-2444
35. Remacle, A. G.; Gawlik, K.; Golubkov, V. S.; Cadwell, G. W.; Liddington, R. C.; Cieplak, P.; Millis, S. Z.; Desjardins, R.; Routhier, S.; Yuan, X. W.; Neugebauer, W. A.; Day, R.; Strongin, A. Y. Selective and potent furin inhibitors protect cells from anthrax without significant toxicity Int. J. Biochem. Cell Biol. 2010, 42 (6) 987-995
36. Tsuji, A.; Sakurai, K.; Kiyokage, E.; Yamazaki, T.; Koide, S.; Toida, K.; Ishimura, K.; Matsuda, Y. Secretory proprotein convertases PACE4 and PC6A are heparin-binding proteins which are localized in the extracellular matrix. Potential role of PACE4 in the activation of proproteins in the extracellular matrix Biochim. Biophys. Acta 2003, 1645 (1) 95-104
37. Khatib, A. M.; Siegfried, G.; Chretien, M.; Metrakos, P.; Seidah, N. G. Proprotein convertases in tumor progression and malignancy: novel targets in cancer therapy Am. J. Pathol. 2002, 160 (6) 1921-1935
38. Rixe, O.; Fojo, T. Is cell death a critical end point for anticancer therapies or is cytostasis sufficient? Clin. Cancer Res. 2007, 13 (24) 7280-7287
39. Houghten, R. A.; Pinilla, C.; Blondelle, S. E.; Appel, J. R.; Dooley, C. T.; Cuervo, J. H. Generation and use of synthetic peptide combinatorial libraries for basic research and drug discovery Nature 1991, 354 (6348) 84-86
40. Fields, G. B.; Noble, R. L. Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids Int. J. Pept. Protein Res. 1990, 35 (3) 161-214
41. 50) of an enzymatic reaction Biochem. Pharmacol. 1973, 22 (23) 3099-3108