Parallel array libraries

A follow-on concept to the one-bead-one-compound concept was recently published as a library of libraries , whereby the authors demonstrated, for peptides, the idea of one-bead-one-motif [83], For linear peptides, this method assumes that some positions are important for structure and some are important for contact with the target. The library construction is accomplished by combining elements of an iterative library with a parallel array library. The construction of the library breaks the structure down into positions defined as structural positions and motif (pharmacophore) positions. The structural positions are built with mixtures of building blocks and the motif positions are constructed through the divide, couple, and recombine procedure. The results reported showed that peptide binding motifs could be identified that reproduced known motifs. 

Figure 14.1 The conceptual difference between the synthesis of a combinatorial library with exponential increase in number of compounds and the synthesis of parallel arrays of discrete compounds.

PARALLEL AND LIBRARY SYNTHESIS OF GLYCOPEPTIDES 14.7.1 Parallel Synthesis of Glycopeptide Arrays... 

A one pot formation and purification of a 5-arylidine 4-thiazolidinone library has also been reported using polymer scavenging as the principle method of purification. An automated synthesizer was employed to make a parallel array of 4080 4-thiazolidinones, prepared simultaneously from a 3-component condensation of mercaptoacetic acid with an amine and a carbonyl compound. Further structural decoration was then introduced using the libraries from libraries principle where the core template was derivatized via an aldol reaction with a second carbonyl unit at the 5-methylene position (Scheme 2.57) [84]. After both synthetic steps. 

Polymer-assisted methodology has been used several times for parallel-array synthesis of libraries involving three to five synthetic steps. Scheme 11 shows a three-step solution-phase synthesis of 2-thioxo-4-dihydro-pyrimid-inones wherein the key purification step involved amine resin 1 to sequester excess aldehydes and isot,hiocyanates from upstream transformations. Thermal cyclization of the purified intermediates gave the desired 2-thioxo-4-dihydropyrimidinones in excellent yields and purities.83... 

Figure 8.1. The conceptual difference between a combinatorial library and parallel arrays of compounds.

Hybrid OpenMP/MPI parallelization is used to compute Hv. The multithreaded OpenMP library is used for parallelization within each node, while MPI is used for communication between nodes. The subroutine fipsi that computes Hv contains two arrays of the same size the results of the portion of the calculation local to a node are stored in hps local, while the results of the portion of the calculation that requires communication are stored in hpsbujf. On each node, a dedicated (master) OpenMP thread performs all the communication, while other threads perform local parts of the work. In general, one uses as many threads as there are processors on a given node. The following scheme presents an overview of the execution of subroutine, hpsi ... 

Parallel processing of synthetic operations has been one of the cornerstones of medicinal and high-throughput synthesis for years. In the parallel synthesis of compound libraries, compounds are synthesized using ordered arrays of spatially separated reaction vessels adhering to the traditional one vessel/one compound philosophy. The defined location of the compound in the array provides the structure of the compound. A commonly used format for parallel synthesis is the 96-well microtiter plate, and today combinatorial libraries comprising hundreds to thousands of compounds can be synthesized by parallel synthesis, often in an automated fashion. 

Here, we present an overview of the aspects of the design, synthesis, analysis, and screening of combinatorial solid-phase glycopeptide libraries as compared to parallel glycopeptide arrays. 

While parallel synthesis of arrays of glycopeptides is readily achieved by implementation of the building-block approach (Scheme 14.1, Strategy 2),101 glycopeptide library synthesis in a combinatorial manner via the split-mix method has yet to prove routine. The difficulty lies in the structural analysis of the vast number of compounds generated in picomolar quantities on a single bead. Whereas peptides on... 

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