Combinatorial libraries molecules

P Willett, J Bradshaw and D V S Green 1999. Selecting Combinatorial Libraries to Optimize rsity and Physical Properties. Journal of Chemical Information and Computer Science 39 169-177. 1 and A W R Payne 1995. A Genetic Algorithm for the Automated Generation of Molecules in Constraints. Journal of Computer-Aided Molecular Design 9 181-202. 

Fig. 1.3 Various small-molecule peptoid ligands derived from combinatorial libraries...

Certain types of molecules, especially polypeptides and polynucleotides, lend themselves to synthesis on solid supports. In such syntheses, the starting material is attached to a small particle (bead) or a surface and the molecule remains attached during the course of the synthetic sequence. Solid phase synthesis also plays a key role in creation of combinatorial libraries, that is, collections of many molecules synthesized by a sequence of reactions in which the subunits are systematically varied to create a range of structures (molecular diversity). 

A combinatorial library of fluorescent NBD molecules was used to visualize subcellular transport pathways in living cells, using a kinetic, high content imaging system to monitor spatiotemporal variations of intracellular probe distribution <2004MI414>. 

The major components are series of homologous trimers, tetramers, and pentamers of the three acids 44-46, along with smaller quantities of dimers, hexamers, and heptamers. Furthermore, the secretion contains several isomers of each oligomer, furnishing a combinatorial library of several hundred macro-cyclic polyamines [51, 52]. Using repeated preparative HPLC fractionation, the most abundant trimeric, tetrameric and pentameric earliest-eluting compounds were isolated. One and two-dimensional H NMR spectroscopic analyses showed that these molecules were the symmetric macrocyclic lactones 48, 49, and 50 (m, n, o, p, q=7) derived from three, four or five units, respectively, of acid 46. Moreover, using preparative HPLC and NMR methods, various amide isomers, such as 53,54, and 55 (Fig. 9) were also isolated and characterized [51,52]. 

There has been significant advancement in the applications of NMR to the development of small-molecule pharmaceutical products. For example, advances in NMR automation (e.g., flow-injection analysis) and directly coupled methods (e.g., LC-MS-NMR analysis) have made analysis and characterization of small-molecule drugs much easier.23 25 These improvements have helped chemists to develop and characterize small-molecule combinatorial libraries and to screen for active compounds.4 6 It is likely some of these techniques can also be used in biopharmaceutical product development. 

Kenseth, J.R. and Coldiron, S.J., High throughput characterization and quality control of small molecule combinatorial libraries, Curr. Opin. Chem. Biol., 8, 418, 2004. 

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