The Solid phase synthesis (SPS) concept, first developed for biopolymers, has spread in every field where organic synthesis is involved. While the potential of the solid-phase method was obvious in 1959 to its discoverer, Prof. R. B. Merrifield, it was unpredictable its dominance in peptide synthesis and especially in combinatorial chemistry, an area not yet conceived. SPS paved the way for solid-phase combinatorial approaches (extensively reviewed in (Choong, I. C. and Ellman, J. A.: 1996, Annu. Rep. Med. Chem. 31, 309–318; Obrecht, D. and Villalgordo, J. M.: 1998, Solid-supported Combinatorial and Parallel Synthesis of Small-Molecular-Weight Compound Libraries. Pergamon Press Ltd., Oxford, UK; Chabala, J. C.: 1995, Curr. Opin. Biotechnol. 6, 632–639; Kamal, A., Reddy, K. L., Devaiah, V., Shankaraiah, N., Reddy, D. R.: 2006, Mini Rev. Med. Chem. 6, 53–69; Whitehead, D. M., McKeown, S. C., Routledge, A.: 2005, Comb. Chem. HTS 8, 361–371; Nefzi, A., Ostresh, J. M., Houghten, R. A.: 1997, Chem. Rev. 97, 449–472; Gordon, E. M., Gallop, M. A., Patel, D. V.: 1996, Acc. Chem. Res. 29, 144–154)) as many laboratories and companies focused on the development of technologies and chemistry suitable to this new methodology. This resulted in the spectacular outburst of combinatorial chemistry, which profoundly changed the approach for new drug discovery. Combinatorial chemistry is currently considered a valid approach for a wide range of biomedical applications, such as, target validation and drug discovery.
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References
Aggarwal S., Harden J. L., Denmeade S. R. (2006) Bioconjug. Chem. 17:335–340
Andrews M. J., McInnes C., Kontopidis G., Innes L., Cowan A., Plater A., et al. (2004) Org. Biomol. Chem. 2:2735–2741, Epub 2004 Sep 9
Ansari S., Helms V. (2005) Proteins Struct. Funct. Bioinform. 61:344–355
Archakov A. I., Govorun V. M., Dubanov A. V., Ivanov Y. D., Veselovsky A. V., Lewi P., et al. (2003) Proteomics 3:380–391
Backes B. J., Ellman J. A. (1997) Curr. Opin. Chem. Biol. 1:86–93
Baum R. M. (1994) Chem. Eng. News 72:20–26
Boger D. L., Desharnais J., Capps K. (2003) Angew. Chem. Int. Ed. 42:4138–4176
Bone R. C. (1995) Crit. Care Med. 23:1313–1315
Bone R. C., Fisher C. J., Clemmer T. P., et al. (1987) N. Engl. J. Med. 317:653–658
Borman S. (1996) Chem. Eng. News 74:29–54
Bradley M. (2002) Curr. Med. Chem. 9:2173–2177
Brase S., Dahmen S. (2000) Chem. Eur. J. 6:1899–1905
Burkoth T. S., Fafarman A. T., Charych D. H., Connolly M. D., Zuckermann R. N. (2003) J. Am. Chem. Soc. 125(29):8841–8845
Canela, N., Orzaez, M., Fucho, R., Mateo, F., Gutierrez, R., Pineda-Lucena, A., et al.: 2006, J. Biol. Chem. 281, 35942–35953
Chabala J. C. (1995) Curr. Opin. Biotechnol. 6:632–639
Cho, J. K., White, P. D., Klute, W., Dean, T. W. and Bradley, M.: 2004, Chem. Comm. 502–503
Choong, I. C. and Ellman, J. A.: 1996, Annu. Rep. Med. Chem. 31, 309–318
Christman J. W., Holden E. P., Blackwell T. S. (1995) Crit. Care Med. 23:955–963
Collins I., Garrett M. D. (2005) Curr. Opin. Pharmacol. 5:366–373
Cremer G. A., Tariq H., Delmas A. F. (2006) J. Pept. Sci. 12:437–442
Cronin L., Cook D. J., Carlet J. et al. (1995) Crit. Care Med. 23:1430–1439
Curran D. P., Wipf P. (1997) Chem. Eng. News 75:6–7
De Luca L., Giacomelli G., Porcheddu A. (2005) J. Comb. Chem. 7:905–908
Dooley C. T., Chung N. N., Wilkes B. C., Schiller P. W., Ramirez-Alvarado M., Blanco F. J., Serrano L. (1996) Nat. Struct. Biol. 7:604–612
Edwards J. V., Caston-Pierre S., Bopp A. F., Goynes W. (2005) J. Pept. Res. 66:160–168
Facchinetti M. M., De Siervi A., Toskos D., Senderowicz A. M. (2004) Cancer Res. 64:3629–3637
Fischer C. J. (1994) JAMA 271:1836–1843
Fischer C. J., Zimmerman J., Khazaeli M. B., et al. (1990) Crit. Care Med. 18:1311–1315
Fischer U., Schulze-Osthoff K. (2005) Cell Death Differ. 12:942–961
Furka A. (1995) Drug Dev. Res. 36:1–12
García-Martín F., Quintanar-Audelo M., Garcia-Ramos Y., Cruz L. J., Gravel C., Furic R., et al. (2006) J. Comb. Chem. 8:213–220
Garibay, P., Toy, P. H., Hoeg-Jensen, T. and Janda, K. D.: 1999, Synlett 9, 1438–1440
Geysen H. M., Barteling S. J., Meloen R. H. (1985) Proc. Natl. Acad. Sci. U. S. A. 82:178–182
Geysen H. M., Meloen R. H., Barteling S. J. (1984) Proc. Natl. Acad. Sci. U. S. A. 81:3998–4002
Gold L., Alper J. (1997) Nat. Biotechnol. 15:297
Gonzalez-Navarro H., Mora P., Pastor M., Serrano L., Mingarro I., Perez-Paya E. (2000) Mol. Divers. 5:117–126
Gordon E. M., Gallop M. A., Patel D. V. (1996) Acc. Chem. Res. 29:144–154
Green D. R., Kroemer G. (2005) J. Clin. Invest. 115:2610–2617
Grotli M., Gotfredsen C. H., Rademann J., Buchardt J., Clark A. J., Duus J. O., et al. (2000) J. Comb. Chem. 2:108–119
Hioki H., Fukutaka M., Takahashi H., Kodama M., Kubo K., Ideta K., et al. (2004) Tetrahedron Lett. 45:7591–7594
Hioki H., Fukutaka M., Takahashi H., Kubo M., Matsushita K., Kodama M., et al. (2005) Tetrahedron 61:10643–10651
Ho Y., Gruhler A., Heilbut A., Bader G. D., Moore L., Adams S. L., et al. (2002) Nature 415:180–183
Houghten R. A. (1985) Proc. Natl. Acad. Sci. U. S. A. 82:5131–5135
Houghten R. A., Pinilla C., Blondelle S. E., Appel J. R., Dooley C. T., Cuervo J. H. (1991) Nature 354:84–86
Humet M., Carbonell T., Masip I., Sanchez-Baeza F., Mora P., Canton E., et al. (2003) J. Comb. Chem. 5:597–605
Kamal A., Reddy K. L., Devaiah V., Shankaraiah N., Reddy D. R. (2006) Mini Rev. Med. Chem. 6:53–69
Kappe C. O. (2000) Bioorg. Med. Chem. Lett. 10:49–51
Kempe M., Barany G. (1996) J. Am. Chem. Soc. 118:7083–7093
Lademann U., Cain K., Gyrd-Hansen M., Brown D., Peters D., Jaattela M. (2003) Mol. Cell Biol. 23:7829–7837
Lam K. S., Salmon S. E., Hersh E. M., Hruby V. J., Kazmierski W. M., Knapp R. J. (1991) Nature 354:82–84
Lam K. S., Lebl M., Krchnak V. (1997) Chem. Rev. 97:411–448
Lamping N., Hoess A., Yu B., Park T. C., Kirschning C. J., Pfeil D., et al. (1996) J. Immunol. 157:4648–4656
Lavrik I. N., Golks A., Krammer P. H. (2005) J. Clin. Invest. 115:2665–2672
Lazo J. S., Wipf P. (2000) J. Pharmacol. Exp. Ther. 293:705–709
Lefering R., Neugebauer E. A. M. (1995) Crit. Care Med. 23:1294–1303
Levin M., Quint P. A., Goldstein B. et al. (2000) Lancet 356:961–967
Li P., Nijhawan D., Budihardjo I., Srinivasula S. M., Ahmad M., Alnemri E. S., et al. (1997) Cell 91:479–489
Linton S. D., Karanewsky D. S., Ternansky R. J., Chen N., Guo X., Jahangiri K. G., et al. (2002a) Bioorg. Med. Chem. Lett. 12:2973–2975
Linton S. D., Karanewsky D. S., Ternansky R. J., Wu J. C., Pham B., Kodandapani L., et al. (2002b) Bioorg. Med. Chem. Lett. 12:2969–2971
Lo Conte L., Chothia C., Janin J. (1999) J. Mol. Biol. 285:2177–2198
Malet G., Martin A. G., Orzaez M., Vicent M. J., Masip I., Sanclimens G., et al. (2006) Cell Death Differ. 13:1523–1532
Martin A. G., Fearnhead H. O. (2002) J Biol. Chem. 277:50834–50841
Masquelin T., Sprenger D., Baer R., Gerber F., Mercadal Y. (1998) Helv. Chim. Acta 81:646–660
Massague J. (2004) Nature 432:298–306
McAllister L. A., McCormick R. A., Procter D. J. (2005) Tetrahedron 61:11527–11576
McMurray J. S. (1998) Biopolymers 47:405–411
Merrifield R. B. (1963) J. Am. Chem. Soc. 85:2149–2154
Mora P., Masip I., Cortés N., Marquina R., Merino R., Merino J., Carbonell T., Mingarro I., Messeguer A., Pérez-Payá E. (2005) J. Med. Chem. 48:1265–1268
Murray A. W. (1987) Nature. 327:14–15
Nefzi A., Ostresh J. M., Houghten R. A. (1997) Chem. Rev. 97:449–472
Nguyen J. T., Wells J. A. (2003) Proc. Natl. Acad. Sci. U. S. A. 100:7533–7538
Obrecht D., Villalgordo J. M. (1998) Solid-supported Combinatorial and Parallel Synthesis of Small-molecular-weight Compound Libraries. Pergamon Press Ltd., Oxford, UK
Pacofsky G. J., Lackey K., Alligood K. J., Berman J., Charifson P. S., Crosby R. M., et al. (1998) J. Med. Chem. 41:1894–1908
Parent J. B., Gazzano-Santoro H., Wood D. M. et al.: (1992) Circ. Shock 38:63–73
Pastor M. T., de la Paz M. L., Lacroix E., Serrano L., Perez-Paya E. (2002) Proc. Natl. Acad. Sci. U. S. A. 99:614–619
Pinilla C. A., Blanc J. R., Houghten R. A. (1992) Biotechniques 13:437–447
Plunkett M. J., Ellman J. A. (1997) Sci. Am. 276:68–73
Porcheddu A., Giacomelli G., De Luca L., Ruda A. M. (2004) J. Comb. Chem. 6:105–111
Radomski M. W., Palmer R. M. J., Moncada S. (1990) Proc. Natl. Acad. Sci. U. S. A. 87:10043–10047
Rapp, W.: 1996, in G. Jung (ed.), Combinatorial Peptide and Nonpeptide Libraries, VCH, Weinheim
Ravn J., Bourne G. T., Smythe M. L. (2005) J. Pept. Sci. 11:572–578
Renil M., Meldal M. (1996) Tetrahedron Lett. 37:6185–6188
Ried C., Wahl C., Miethke T., Wellnhofer G., Landgraf C., Schneider-Mergener J., et al. (1996) J. Biol. Chem. 271:28120–28127
Roice M., Pillai V. N. R. (2005) J. Polym. Sci. Part A, Polym. Chem. 43:4382–4392
Rombouts F. J. R., Fridkin G., Lubell W. D. (2005) J. Comb. Chem. 7:589–598
Rual J. F., Venkatesan K., Hao T., Hirozane-Kishikawa T., Dricot A., Li N., et al. (2005) Nature 437:1173–1178
Sáez-Llorens X., McCracken G. H. (1993) J. Pediator. 123:497–508
Salmon S. E., Lam K. S., Lebl M., Kandola A., Khattri P. S., Wade S., et al. (1993) Proc. Natl. Acad. Sci. U. S. A. 90:11708–11712
Sanchez-Martin R. M., Mittoo S., Bradley M. (2004) Curr. Topics Med. Chem. 4:653–669
Sandhu C., Slingerland J. (2000) Cancer Detect Prev. 24:107–118
Schumann R. R., Latz E. (2000) Chem. Immunol. 74:42–60
Schumann R. R., Leong S. R., Flaggs G. W., Gray P. W., Wright S. D., Mathison J. C., et al. (1990) Science 249:1429–1431
Sebestyen F., Dibo G., Kovacs A., Furka A. (1993) Bioorg. Med. Chem. Lett. 3:413–418
Sebolt-Leopold J. S., English J. M. (2006) Nature 441:457–462
Senderowicz A. M. (2002) Oncologist 7:12–19
Senderowicz A. M. (2003) Cancer Biol. Ther. 2:S84–95
Senderowicz A. M. (2005) Prog. Drug Res. 63:183–206
Service R. F. (1996) Science 272:1266–1268
Shapiro G. I., Koestner D. A., Matranga C. B., Rollins B. J. (1999) Clin. Cancer Res. 5:2925–2938
Shapiro L., Gelfand J. A. (1993) New Horiz 1:13–22
Silverman, H. and Owen M. J.: 1998, Bactericidal Endotoxin in Human Disease. XOMA Ltd, pp. 1–28
Stein L. D. (2004) Nature 431:915–916
Suffredini A. (1994) Crit. Care Med. 22:S12–18
Tamborini E., Bonadiman L., Greco A., Albertini V., Negri T., Gronchi A., et al. (2004) Gastroenterology 127:294–299
Ulevitch R. J., Tobias P. S. (1999) Curr. Opin. Immunol. 11:19–22
Vallance P. M. S. (1993) New Horiz. 1:77–86
Poll T. Van der (2001) Lancet Infect. Dis. 1:165–174
Vicent M. J., Perez-Paya E. (2006) J. Med. Chem. 49:3763–3765
Wang X., Zhu S., Drozda M., Zhang W., Stavrovskaya I. G., Cattaneo E., et al. (2003) Proc. Natl. Acad. Sci. U. S. A. 100:10483–10487
Whitehead D. M., McKeown S. C., Routledge A. (2005) Comb. Chem. HTS 8:361–371
Yu Z. R., Bradley M. (2002) Curr. Opin. Chem. Biol. 6:347–352
Yu X., Acehan D., Menetret J. F., Booth C. R., Ludtke S. J., Riedl S. J., et al. (2005) Structure (Camb.) 13:1725–1735
Zheng T. S., Hunot S., Kuida K., Momoi T., Srinivasan A., Nicholson D. W., et al. (2000) Nat. Med. 6:1241–1247
Ziegler E. J. (1991) N. Engl. J. Med. 324:429–436
Acknowledgments
This work was supported by grants from Spanish Ministry of Science and Education (MEC) (BIO2004-998), Fundación Centro de Investigación Príncipe Felipe and a Marie Curie Reintegration grant (ERG-2004-06307). M. Orzáez thanks Bancaja for a postdoctoral fellowship. L. Mondragón is supported by a FPI fellowship from MEC.
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Orzáez, M., Mora, P., Mondragón, L. et al. Solid-phase Chemistry: A Useful Tool to Discover Modulators of Protein Interactions. Int J Pept Res Ther 13, 281–293 (2007). https://doi.org/10.1007/s10989-007-9079-y
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DOI: https://doi.org/10.1007/s10989-007-9079-y