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Solid-phase Chemistry: A Useful Tool to Discover Modulators of Protein Interactions

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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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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Correspondence to María J. Vicent.

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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).

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  • solid-phase synthesis
  • protein–protein interactions
  • protein–lipid interactions
  • apoptosis
  • cancer
  • sepsis