Library chemical peptide

Screening for biologic activity of large numbers of natural products banks of previously discovered chemical entities and large libraries of peptides, nucleic acids, and other organic molecules... 

Another decoration pool library L23 was reported by Nestler (49), who presented the appendage of a peptidic chain to the two hydroxylic functions of a steroid scaffold (Fig. 4.15). The library was made up of 10 x 10 x 10 x 10 = 10,000 individuals using a chemical encoding method (39) and L-a-amino acids as monomer sets (R1-R4). The assay of the library as a source of artificial two-armed receptors for enkephalin-related peptides produced positives with micromolar affinity. Much larger libraries could be obtained by simply increasing the monomer sets and the length of the two arms this could lead to a primary library of peptide-binding artificial receptors similar scaffolds have been repeatedly exploited for combinatorial purposes (50-52). 

Finally, the concept of libraries from libraries [11—13] utilizes a chemical transformation on a library of peptides to yield a nonpeptide library. This is done while the library compounds are attached to the resin support. An example of this approach is given in Fig. 4. When applied intelligently, this technique can increase the number of library members at a geometric rate. 

FIGURE 2.10 ACE-UV clectrophcrograms of the 1 jnoc-l)l)X X2 library (100 peptides) (A) without, and (B) with vancomycin. See text for discussion. (Reprinted from Chu et al. [87], used with permission. Copyright 1996 by the American Chemical Society.)... 

At the beginning, permethylated peptide libraries were derived by a post-modification of peptide libraries attached to the solid-phase support. The amide bond functionalities were alkylated using a solution of sodium hydride in dimethylsulfoxide, followed by addition of neat methyl iodide, therefore generating libraries from libraries . A peptide library that underwent this simple chemical transformation was used to identify compounds with potent antimicrobial activity against Gram-positive bacteria [21]. 

SI Cho, W Zheng, A Tropsha. Rational combinatorial library design 2. Rational design of targeted combinatorial peptide libraries using chemical similarity probe and the inverse QSAR approaches. J Chem Inf Comput Sci 38 259-268, 1998. 

Menifield s concept of a solid-phase method for peptide synthesis and his development of methods for canying it out set the stage for an entirely new way to do chemical reactions. Solid-phase synthesis has been extended to include numerous other classes of compounds and has helped spawn a whole new field called combinatorial chemistry. Combinatorial synthesis allows a chemist, using solid-phase techniques, to prepare hundreds of related compounds (called libraries) at a time. It is one of the most active areas of organic synthesis, especially in the pharmaceutical industry. 

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. 

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