Natural combinatorial libraries

Kingston DGl, Newman DJ. (2002) Mother s nature combinatorial libraries Their influence on the synthesis of drugs. Curr Opin Drug Discovery Dev 5 304-316. 

FIGURE 11.1 Natural combinatorial libraries from (a) Epilachna borealis (From Schroder, F.C. et al., A combinatorial library of macrocycUc polyamines produced by a ladybird beetle, J. Am. Chem. Soc., 122, 3628, 2000) (b) Landolphia dulcis. (From Staerk, D. et al.. Isolation of a bbrary of aromadendranes from Landolphia dulcis and its characterization using the VolSurf approach, J. Nat. Prod., 67, 799, 2004.)... 

Lee, M.L. Schneider, G. (2001) Scaffold Architecture and Pharmacophoric Properties of Natural Products and Trade Drugs Application in the Design of Natural Product-Based Combinatorial Libraries. Journal of Combinatorial Chemistry, 3, 284-289. 

Donia, M.S., Hathaway, B.J., Sudek, S. et al. (2006) Natural combinatorial peptide libraries in cyanobacterial symbionts of marine ascidians. Nature Chemical Biology, 2, 729. 

Fig. 10.6 Concept of multitarget affinity specificity screening (MASS). Macromolecular targets (typically structured RNA constructs or proteins) in nondenaturing buffers are mixed in solution with a collection of potential ligands derived from natural product fractions, combinatorial libraries, or other diverse compound collections. The...

Once binding hot spots are identified by DXMS analysis, combinatorial libraries can be generated, based in part on structural information available that may suggest the nature of the peptidic features of the interacting proteins that... 

For the purpose of organizing this stereoselecfion chapter, we will summarize the fiterature using the following taxonomy first divided by the nature of the guest and second by the nature of the dynamic combinatorial library (DCL) components. 

Lee ML, Schneider GJ. (2001) Scaffold architecture and pharmaco-phoric properties of natural products and trade drugs Application in the design of natural product-based combinatorial libraries. Comb Chem 3 284-289. 

Abreu PM, Branco PS. (2003) Natural product-like combinatorial libraries. J Braz Chem Soc 14 675-712. 

Figure 6. Distributions of essential computed molecular properties defining drug-likeness for selected compound sets. Shown are the fraction of compounds vs. the properties. Orange NIBR historical medicinal chemistry collection. Brown Compilation of combinatorial chemistry libraries. Dark Green Drugs (launched or Phase III listed in MDDR or CMC). Brown Compilation from combinatorial libraries. Pink Natural products of DNP. tight Green HTS hits of NIBR 2004 screens. All properties were calculated with Pipeline Pilot software www.scitegic.com).

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