Combinatorial chemistry tripeptides

Saito, K., Jin, D., Ogawa, T., Muramoto, K., Hatakeyama, E., Yasuhara, T., and Nokihara, K. (2003). Antioxidative properties of tripeptide libraries prepared by the combinatorial chemistry. J. Agric. Food Chem. 51, 3668-3674. 

Yamashita and Weinstock [62], Scott et al. [63, 64] and Egner et al. [65] reported the use of fluorophores in combinatorial chemistry and, in particular, as tags for pool library encoding. Multiple fluorophores were pre-encoded at a very low loading level (>0.1%) and the codes were read via various fluorimetric detection techniques [63]. Small tripeptide libraries were tested and decoded with success [62], but many potential drawbacks were also highlighted [63] so that a careful assessment of all the relevant variables (solid support... 

Early reported applications of this technique were the preparation of a 24-member peptide library [83], of a 125-member tripeptide-substituted cinnamic acid library tested for inhibition of tyrosine phosphatase PTP1B [83], of a 64-member peptide-like library [83] and of libraries based on a natural product, epothilone, using also new polystyrene grafted solid supports [84], Other applications, ranging from l,5-benzodiazepin-2-one library synthesis [85] to chalcone library synthesis [86], were also recently reported. Commercialization of the basic components for this technique [87] (reaction supports and vessels, tags, software, sorters, reaction stations, and so on) will ensure its quick and effective use in combinatorial chemistry and also the implementation of new technical features and possibilities for more complex and demanding applications in future. 

There are some examples of the use of HPLC-NMR in combinatorial chemistry. A synthetic mixture of 27 closely related tripeptides [23] formed from all the combinations of alanine (A), methionine (M) and tyrosine (Y), as the C-terminal amide could be resolved and characterized with the help of this methodology (REF is given in 24 which is listed at the end). Based on chemical shifts and peak multiplicities, the on-flow HPLC-NMR characterization of the majority of the components of the mixture was achieved. This application demonstrated that this approach is likely to be an effective method for compounds mixtures. 

Metz G, Ottleben H, Vetter D. Small molecule screening on chemical microarrays. Meth. Princ. Med. Chem. 2003 19 213-236. Ladame S. Dynamic combinatorial chemistry on the road to fulfilling the promise. Org. Biomol. Chem. 2008 6 219-226. Hioki H, Still WC. Chemical evolution a model System that selects and amplifies a receptor for the tripeptide D-Pro-L-Val-D-Val. J. Org. Chem. 1998 63 904-905. 

The addition of cyanide to imine (Strecker-type reaction) can also be catalyzed by chiral Ti complexes. In a pioneering work reported by Snapper and Hoveyda, a series of titanium complexes of tripeptide-based Schiffbase ligands have been discovered by combinatorial chemistry approach for the addition of TMSCN to imine derivatives with >93% conversion of substrates and excellent enantioselectivities (85-97% ee) [227]. This methodology has provided a practical procedure for the... 

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