Oligopeptide libraries

Shibata et al. (213) prepared and screened an SP oligopeptide library for its ability to complex cobalt ions, isolating several high-binding sequences. 

Among other published reports, Gilbertson et al. [70] prepared a 63-mem-ber supported phosphine-containing oligopeptide library whose members were... 

Library of Cyclic Oligopeptides as Additives to Background Electrolyte for Chiral Capillary Electrophoresis... 

A very similar cloning strategy has been used for the 48-kDa subunit of the glycine-receptor channel by Betz and collaborators [4]. Strychnine was used as an affinity ligand, and synthetic oligopeptides were constructed from the purified material. They have been used to screen cDNA libraries. 

In the following I will present a model to tackle this question. We are at the level of speculations, but we will use some known facts. For example, let s start from the condensation of NCA-anhydrides, a reaction which, as we have seen in the previous chapter, is considered prebiotic. In this way, oligopeptides up to (say) a length of ten can be built, possibly under thermodynamic control, but starting from a definite set of conditions (amino-acid composition in the starting mixture, pH, salinity, etc.). We can assume, and this is actually quite reasonable, that in this way copious libraries of different decapeptides have been formed, each in a significant concentration. 

Once we have this library, fragment-condensation procedures might link the oligopeptides to one another so as to build longer chains. Prebiotic methods for fragment condensation are not really known. Kent s synthesis comes close to the target (Kent, 1999) but is restricted to particular chemical structures and cannot be seen as a generalized prebiotic method. 

Let us see where this scheme may bring us, and for this purpose refer to Figure 4.7. This shows a small library of oligopeptides, where one (or more) of these products, indicated in the figure with an asterisk, is endowed with peptidase activity. These peptides then, under the reaction conditions, can catalyze fragment condensation in a specific way - for example of those peptides with a terminal aromatic residue. Following the first condensation step, the catalytic center is inserted into a longer polypeptide, with retention of the catalytic activity. 

Felici, F., Castagnoli, L., Musacchio, A., Jappelli, R., and Cesareni, G. (1991) Selection of antibody ligands from a large library of oligopeptides expressed on a multivalent exposition vector. J. Mol. Biol. 222, 301-310. 

Reactivity within (DL)-PheNCA crystals provides a number of simple ways to de-symmetrize the racemic mixtures of the homochiral oligopeptides. For example, L-2-(thienyl)-alanineNCA (ThieNCA) molecules have been shown to enantioselectively occupy the L-sites in the DL-PheNCA host crystals. Lattice-controlled polymerization of such D-Phe/(L-Phe L-Thie)-NCA mixed crystals yields libraries of non-racemic oligopeptides of ho-... 

The newly available biological high-throughput screening (HTS) systems have induced many initiatives in the field of combinatorial chemistry [42]. Besides oligopeptide syntheses [43], multicomponent reactions offer attractive methods for the production of high-diversity libraries. Passerini and Ugi reactions (Scheme 19) are frequently used for synthesis of libraries containing thousands of compounds [44],... 

Poulter and Rine carried out an extensive investigation into the substrate specificity in the two yeast splice variants of the protease, Reel and Afcl [19]. The authors generated a -CaaX library originating from the a-factor oligopeptide, with modifications at each of the ai, a2, and X positions. For each of the splice variants, there was a distinct preference for specific residues at each of the positions. Additionally, there were also library members that were capable of only undergoing proteolysis by one of the enzymes. Despite a sequence similarity between the two splice variants, it appeared that they each possessed unique amino acid preferences however, some overlap was observed. Poulter and coworkers also synthesized CaaX peptides from both yeast and mammalian proteins to further characterize the enzymatic activity of Reel [20], While both farnesylated and... 

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