Library cinnamic acid

Library one contained 12 different structures (recall that there were originally three different phenanthridinones and four different cinnamic acids). The first deconvolution step of the approach is shown in Figure 9. Here, only the CN position was randomized, and the PH moieties were specific. This led to the preparation of three new libraries of 4 compounds each. Receptor binding was again performed as before and only one of these three new sublibraries showed affinity for the receptor at 10 p/lf(Figure 8b). The final step in the process required to elucidate the active component(s) was to synthesize and purify each of the 4 members of this library as shown in Figure 9. Receptor binding on these... 

SC = straight chain, CN = cinnamic acid. Each library was tested at 1 pnM and 10 nM. Results were compared to cold bradykinin binding, which was tested at two lower concentrations, 0.1 nM and 1 nM. Panels (b) and (c) correspond to the receptor binding results obtained using the two breakdown steps from original library number 1, as shown in Figure 9. 

Moran, E. J. Sarshar, S. Cargill, J. F. Shahbaz, M. M. Lio, A. M. Mjalli, A. M. M. Armstrong, R. W. Radio Frequency Tag Encoded Combinatorial Library Method for the Discovery of Tripeptide-Substituted Cinnamic Acid Inhibitors of the Protein Tyrosine Phosphatase PTP1B, J. Am. Chem. Soc. 1995, 777,10787. 

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],... 

Moran EJ, Sarshar S, Cargill JF, Shahbaz M, Lio A, Mjalli AMM, Armstrong RW, Radiofrequency tog encoded combinatorial library method for the discovery of tripeptide-substituted cinnamic acid inhibitors of the protein tyrosine phosphatase PTPSB J. Am. Chem. Soc., 117 10787-1788, 1995. 

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. 

EJ Moran, S Sarshar, JF Cargill, MM Shahbaz, A Lio, AMM Mjalli, RW Armstrong. Radio frequency tag encoded combinatorial library method for discovery of tri peptide-substituted cinnamic acid inhibitors of the protein tyrosine phosphatase PTP1B. J Am Chem Soc 117 10787-10788, 1995. 

A library of cinnamic acid derivatives was prepared on solid phase using a four-component Ugi condensation [429], The results from screening compounds against the hematopoietic protein tyrosine phosphatase (HePTP) indicate that the variations in R2 has a more pronounced effect on potency than do changes in R1. The most potent compound in the series was found for Rl=phenyl and R2=benzyl (library 44 IC50 3.9 //M) [429],... 

Cinnamic acid 4-hydroxylase from Helianthus tuberosus (Jerusalem artichoke) was the first plant P450 to be functionally characterized. CYP73A1 was designated as the first member of the CYP73 family. This cDNA was isolated from an expression library using antibodies raised against the isolated P450 protein (Section 3.5). Cinnamic acid... 

Similarly, a 20-membered ring of a tetrapeptide derivative containing a 3-substituted cinnamic acid template was closed on a solid support [593]. This methodology was also applied in the synthesis of a small library (15 examples) of cyclic RGD mimics having a diverse array of amino acids, with a variety of ring sizes [594]. 

Library 2.4 Peptidyi cinnamic acid Size 125 members Affiliation Armstrong, R. W. et al. [38] Year 1995... 

As an example of this technology, a library of 125 cinnamate capped tripeptides was synthesized on Rink resin [17] using five amino acid building blocks per coupling step (Scheme 5) [ 16], This library was screened against the human protein tyrosine phosphatase PTP1B enzyme and a number of potent inhibitors were identified (40 nMtechnique based on microchips to which information is written before each chemical step [18],... 

Synthesis of the isoxazoline library [59] was performed on 2-chlorotritylchloride resin. The resin was loaded with diethylphosphonoacetic acid and the polymer-bound phospho-nate reacted with aldehydes to yield substituted E-cinnamic esters or substituted E-acrylic esters. This was followed by a 1,3-dipolar cyclo-addition with nitrileoxides, synthesized via the method of Mukaiyama and Floshinoc [60] (Fig. 17.18). In this reaction, two regioi-somers are formed, each of which exist in two enantiomeric forms. Table 17.4 shows the building blocks used in the library synthesis. 

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