Peptide-based libraries

A peptide based library of RabGGTase inhibitors was reported by Guo et al. [39]. and Tan et al. [26] loosely based on the FTase inhibitor Pepticinnamin E (12, Table 8.2). This library containing 469 peptides was screened using an in vitro fluorometric Rab prenylation assay [40], employing a fluorescent analoge of GGPP, named NBD-FPP, as the prenyl... 

Scheme 36.10 Enantioselective hydrogenation using libraries of peptide-based rhodium catalysts.

In 1998, Jacobsen and Sigman demonstrated that peptide-based ligands, such as the one shown in Eq. (1), can be used to access optically enriched amino nitriles. The identity of the optimal catalyst was determined through examination of parallel libraries of catalyst candidates [2], Later, it was demonstrated that this protocol may be extended to additions to ketoimines, affording tertiary amino nitriles in high enantioselectivities [3]. 

As shown in Eq. (4), parallel screening of ligand libraries has allowed us to establish that a closely related peptide-based phosphine ligand promotes the catalytic asymmetric conjugate addition of alkylzincs to nitroalkenes [14]. Not only are the corresponding alkyl nitrones obtained efficiently and in high diaster-eo- and enantioselectivity, appropriate acid workup can deliver the derived ketone directly. 

A variety of unfunctionalized secondary alcohols, including saturated and unsaturated carbinols, are resolved by catalyst 25 with moderate to high selectivi-ties (fcrei=4 to >50, see Scheme 5) [25]. Octapeptide 25 was discovered by screening a split-pool library of peptide catalyst candidates for acylation of 1-phe-nylethanol (3), using a reactivity-based fluorescence screen [26], followed by structure optimization with directed libraries. While substrates with increased steric bulk about the alcohol are resolved with highest selectivities, even 2-butanol is resolved with modest selectivity (fcrei=4). Peptide-based catalysts have also been applied to the resolution of tertiary alcohols, a relatively unexplored area of nonenzymatic asymmetric acylation catalysis [27-29], By using a fluores-... 

Radionuclide-based screening for protein kinase substrates is a quick and effective method for determining peptide substrates for protein kinases.28-31 The method presented here is based on the screening of random synthetic combinatorial peptide libraries with a protein kinase and is divided into two main parts (1) the phosphorylation of the peptide bead library and (2) the recovery and characterization of positive beads. 

What is discussed in this chapter is the situation of plant proteomics in terms of low-abundance proteins. Here is especially described a recent technology, along with dedicated applications, based on a unique sample treatment using combinatorial peptide ligand libraries (CPLL) that have already largely demonstrated their capabilities for novel discovery in animal protein science (2). The situation of both plant-derived food and drinks is reviewed throughout the context of plant proteomics. 

Meloen, R., Timmerman, P., and Langedijk, H. (2004) Bioactive peptides based on diversity libraries, supramolecular chemistry and rational design A class of peptide drugs. Introduction. Mol. Diversity 8, 57-59. 

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. 

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