Chemistry, combinatorial INDEX

B. A. Bunin, The Combinatorial Index. Academic Press, New York, 1998. G. Yung, Combinatorial Chemistry Synthesis, Analysis, Screening. Wiley-VCH, Weinheim, 1999. 

Jung, G. (ed.). Combinatorial Peptide and Nonpeptide Libraries A Handbook. VCH, Weinheim New York, 1996 Bunin, B.A. (ed.). The Combinatorial Index. Academic Press, San Diego. 1998 Gordon, E.M., Kerwin, J.F.J., Combinatorial Chemistry and Molecular Diversity in Drug Discovery, John Wiley Sons, New York, 1998 Terretl, N.K., Combinatorial Chemistry. Oxford University Press, New York, 1998 Moos, W.H., Pavia, M.R., Kay, B.K., Ellington, A.D., Annual Reports in Combinatorial Chemistry and Molecular Diversity. ESCOM, Leiden, 1997. 

Pirrung, M.C., Chau, J.H.-L., and Chen, J., Indexed combinatorial libraries nonoligomeric chemical diversity for the discovery of novel enzyme inhibitors, in Combinatorial Chemistry, Wilson, S.R. and Czarnik, A.W., Eds., Wiley, New York, 1997, pp. 191-206. 

Pirrung MC, Chau JHL, Chen J, Discovery of a novel tetrahydroacridine acetylcholinesterase inhibitor through an indexed combinatorial library, Chemistry Biology, 2 621-626, 1995. 

Tratch, S.S., Devdariani, R.Q. and Zefirov, N.S. (1990a). Combinatorial Models and Algorithms in Chemistry. Topological-Configurational Analogs of the Wiener Index. Zh.Org.Khim., 26, 921-932. 

Tratch, S.S., Stankevitch, I.V. and Zefirov, N.S. (1990) Combinatorial models and algorithms in chemistry. The expanded Wiener number- a novel topological index. J. Comput. Chem., 11, 899-908. 

Figure 3.1. A comparison of (a) traditional chemistry with three approaches to combinatorial chemistry (b) array synthesis directly identifies an active compound (c) one-pot simultaneous synthesis necessitates deconvolution and (d) indexed library indirectly indicates active compounds.

One object of mathematical chemistry is to associate a unique index to each skeleton (i.e., no hydrogen atoms) molecular diagram (Balaban 1973 King 1977 Randic 1992). The index may be a number, a set of numbers, or a matrix. Hydrogen and other atoms with various valences have since been included and three-dimensional or knotted structures have been treated. In the meantime, however, combinatorial chemistries have accumulated so rapidly that the prospect may be for them to outpace the progress in correlating data to one or another index unless a breakthrough occurs in the latter. 

M. Wigler, W.C. Still, Complex synthetic chemical libraries indexed with molecular tags, Proc. Natl. Acad. Sri. U.S.A. 1993, 90,10922 (b) H.P. Nestler, P.A. Bartlett, W.C. Still, A general method for molecular tagging of encoded combinatorial chemistry libraries, J. Org. Chem. 1994, 59, 4723. 

Another paper using the same strategy as the RECAP work looks at the scaffolds present in natural products as a potential source of building blocks for combinatorial chemistry. They broke down the Bioscreen NP database to find all the ring fragments that did not occur in the World Drug Index. The approach... 

Research continues into new and. specialized chemical representations. At the level of indexes, the venerable concept of molecular ID numbers has re.surfaced as a critical component in a 3D chemical diversity partitioning scheme, in addition, hierarchical fragment indexes have been implemented with a tremendous enhancement in search performance. The primary driver for the introduction of new representations is the recent focus on the needs of combinatorial chemistry for library design, specification, storage and retrieval. Noteworthy examples are CHUCKLES and CHORTLES, both extensions of SMILES the former supports the representation of peptide and peptoid sequences on both the monomer and atomic levels, and the latter allows the representation of mixtures as simple strings of characters. 

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