Tripeptide libraries

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. 

The concept of tweezer-like two-armed molecules was used to construct synthetic receptor molecules based on methylene sulfonamide peptidomimetics.11291 When screened for binding against an encoded tripeptide library, one of the synthetic receptors demonstrated a remarkable binding selectivity 11291 the synthetic receptor affinity could be further increased by varying the hinge part of the peptidomimetic molecule.11301... 

The feasibility of the method was demonstrated by testing the members of a tripeptide library for their ability to catalyze the acylation of an alcohol (reactant A) by a dye-marked pentafluorophenyl (Pfp) ester (reactant B). 

In a similar approach, a pretuned glass encased microchip set to emit a unique binary code is placed in a polypropylene tea bag loaded with polystyrene beads. Using a modified split synthesis approach, a 125-membered tripeptide library N-capped as the /r-carboxy-cinnamic acid amide was prepared on Rink resin. Each porous reactor contained a radio frequency transporter which successfully defined the structure of two inhibitors of protein tyrosine phosphatase [37],... 

In order to determine the sequence of the bioactive tripeptide, all the nine sub-libraries need to be tested. If those marked with + are the active ones in screening (H, G and C), then the sequence of the bioactive peptide (from N to C terminal) is white black gray. In deconvolution of a tripeptide library prepared from 20 amino acids, for example, 60 sub-libraries have to be synthesized and screened. For screening of hexapeptides, a set of 120 sub-libraries is needed. Once the set of sub-libraries is prepared in sufficient quantity, it can be used in many different screening experiments. 

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... 

Tseng, M. C. Chu, Y. H., Using surface plasmon resonance to directly identify molecules in a tripeptide library that bind tightly to a vancomycin chip. Anal. Biochem. 2005, 336, 172-177... 

Soo Yoon et al. [32] presented a 50,625-member N-acylated tripeptide library with the structure RESIN-CH2NHCO(CH2)5NH-AA,-AA2-AA3-COR AA, 2 3 were 15 l- or D-amino acids and RCOX were 15 acylating agents. The structure of the haloaromatic tags used, composed by an electrophone tag and by a photosensitive linker, is reported in Figure 5 together with their synthetic pathway. 

In the N-acylated, 50,625-member tripeptide library [32], each monomer position (AA, 2 3 and RCOX) was coded by four tags using a the binary code shown in Figure 6. The null code 0000 was excluded, to have always at least... 

Table 93. Building Blocks and Tags of Tripeptide Library...

G. Subra, L. Soulere, P. Hoffman, C. Enjalbal, J. Martinez, Parallel and mixture combined approach rapid cheap synthesis and characterization of a4096-tripeptides library. QSAR Comb. Sci. 2003, 22, 646-651. 

Tripeptide libraries have shown activity against certain G-protein coupled receptors. For example, screening a library of ca. 221 000 tripeptides (library 3.19) furnished the potent and selective melanocyte-stimulating hormone agonist, H-D-Trp-Arg-Leu-NH2 (IC50 = 620 nM) [62]. A vasopressin-2 receptor antagonist, H-D-Tic-D-Tyr-D-(4-nitro)-Phe-OH (IC50 = 63 nM), was revealed in a second independently prepared tripeptide library construct (library 3.21 15 625 members) [51]. 

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