Looking into the combinatorial chemistry literature one can see that it is still mostly believed that the first combinatorial synthesis was invented by several groups exactly at the same time. In fact the principles of combinatorial chemistry, that is, synthesis of large number, even millions, of compounds and then by applying a proper deconvolution method identify the useful components, was invented, first described and notarized as early as 1982 by the Author of this article. The first publication of the synthetic method was in 1988. In February 1990 the manuscript of an article also describing the combinatorial split-mix synthesis was submitted to the International Journal of Peptide and Protein Research that appeared after a one and a half year delay. In this period four patent applications were filed, two conference lectures, two Nature papers and a book chapter were submitted then published. The editor in chief of the mentioned journal was among the authors of one patent application, one lecture, one Nature article and a book chapter. The evidences described below will hopefully convince the readers that the inventions in the patent submissions and in the mentioned publications were all 2-3 years earlier described in our 1988 publications and these publications were known by the authors.
Facts from the Early Years of the History of Combinatorial Chemistry, Science Journal of Chemistry.
Vol. 6, No. 6,
2018, pp. 123-130.
L. B. Smillie, Á. Furka, N. Nagabhushan, K. J. Stevenson, C. O. Parkes, “Structure of chymotrypsinogen B compared with chymotrypsinogen A and trypsinogen,” Nature, vol. 218, p. 343, 1968.
R. B. Merrifield, “Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide.” J. Am. Chem. Soc. vol. 85, pp. 2149-54, 1963.
Á. Furka, “Combinatorial Chemistry 20 years on..,” DDT, vol. 7, pp. 1-4, 2002.
Á. Furka, F. Sebestyén, M. Asgedom, G. Dibó, “CORNUCOPIA OF PEPTIDES BY SYNTHESIS,” In Highlights of Modern Biochemistry, Proceedings of the 14th International Congress of Biochemistry Prague. VSP. Utrecht.1988, vol. 5, p. 47.
Á. Furka, F. Sebestyén, M. Asgedom, G. Dibó, “MORE PEPTIDES BY LESS LABOUR,” Proceedings of the 10th International Symposium of Medicinal Chemistry, Budapest, Hungary. 1988, p. 288.
R. E. Offord, “Electrophoretic mobilities of peptides on paper and their use in the determination of amide groups,” Nature, vol. 211, pp. 591-3, 1966.
Á. Furka, F. Sebestyén, J. Gulyás In Proc. 2nd Int. Conf. Biochem. Separations, Keszthely, Hungary, 1988, p. 35.
Á. FURKA, F. SEBESTYÉN, M. Asgedom, G. Dibó, “General method for rapid synthesis of multicomponent peptide mixtures.” Int J Peptide Protein Res vol. 37, pp. 487-93, 1991.
K. S. Lam, S. E. Salmon, E-M. Hersh, F. Al-Obeidi, V. J. Hruby, “Rapid selection and structure determination of acceptor binding ligands from a large synthetic peptide library.” Abstr. 12th American Peptide Symposium, Boston, USA. 1991, LW3.
R. A. Houghten, “New approaches for peptide and peptide-mimetic biomedical drug discovery.” Innovation & Perspectives in Solid Phase Synthesis & Related Technologies, Second International Symposium, Canterbury. 1991, 10c.1.
K. S. Lam, S. E. Salmon, E. M Hersh, V. J. Hruby, W. M. Kazmierski & R. J. Knapp, “A new type of synthetic peptide library for identifying ligand-binding activity.” Nature, vol. 354, pp. 82 ‑4, 1991.
R. A. Houghten, C. Pinilla, S. E. Blondelle, J. R. Appel, C. T. Dooley, and J. H. Cuervo, “Generation and use of synthetic peptide combinatorial libraries for basic research and drug discovery.” Nature, vol. 354, pp. 84-6, 1991.
V. J. Hruby, S. D. Sharma, N. T. Collins, T. O. Matsunaga, K. C. Russel, “Application of Peptides.” In: G. A. Grant, editor. “Synthetic Peptides A User's Guide.” Freeman WH and Company, New York 1992 p. 270-272.
Lam KS, Salmon SE, Hersh EM, Hruby VJ, Kazmierski WM & Knapp RJ. A new type of synthetic peptide library for identifying ligand-binding activity. Nature 1992, 358; 434.
Lam KS, Salmon SE, Hersh EM, Hruby VJ, Kazmierski WM & Knapp RJ. “A new type of synthetic peptide library for identifying ligand-binding activity.” Nature, Vol. 360, p. 768, 1992.
R. A. Houghten, “General method or the rapid solid-phase synthesis of large numbers of peptides: Specificity of antigen-antibody interaction at the level of individual amino acids.” Proc Natl Acad Sci US, vol. 82, pp. 5131-5, 1985.
M. Lebl, V. Krchnak, N. F. Sepetov, B. Seligmann, P. Strop, S. Felder, K. S. Lam, “One-Bead-One-Structure Combinatorial Libraries.” Biopolymers. Peptide Science 1995, vol. 37, pp. 177-198.
M. Stankova, S. Wade, K. S. Lam and M. Lebl, “Synthesis of Combinatorial Libraries with Only One Representation of Each Structure.” Peptide Research, vol. 7, pp. 292-298, 1995.
J. A. Smith, J. G. R. Hurrel, S. J. Leach, “A novel method for delineating antigenic determinants: Peptide synthesis and radioimmunoassay using the same solid support.” Immunochemistry, voé. 14, pp. 565-568, 1977.
R. Liu, X. Li and K. S. Lam KS, “Combinatorial chemistry in drug discovery.” Curr Opin Chem Biol, vol. 38, pp. 117–126, 2017.
Á. Furka, “Letter to the Editor.” Curr. Opin. Chem. Biol. vol. 42, p. 186, 2018.
Á. Furka, “Letter to the Editor.” Adv. Drug Deliv. Rev. vol. 125 p. 151, 2018.
Á. Furka, “Comment on ‘Screening and identification of mimotopes of the major shrimp allergen tropomyosin using one- bead-one compound peptide libraries” Cellular & Molecular Immunology, 2018. DOI 10.1038/s41423-018-0173-1.
K. S. Lam, Reply to the “Letter to the Editor” Curr. Opin. Chem. Biol. vol. 42, p. 187, 2018.
R. Liu, X. Li, W. Xiao, K. S. Lam, “Corrigendum to ‘Tumor-targeting peptides from combinatorial libraries“[Adv Drug Deliv Rev. vol. 110–111, pp. 13–37, 2017] DOI 10.1016/j.addr.2018.02.005.