Use Of Combinatorial Libraries Research Articles

In vitro and direct in vivo testing of mixture-based combinatorial libraries for the identification of highly active and specific opiate ligands

The use of combinatorial libraries for the identification of novel opiate and related ligands in opioid receptor assays is reviewed. Case studies involving opioid assays used to demonstrate the viability of combinatorial libraries are described. The identification of new opioid peptides composed of L-amino acids, D-amino acids, or L-, D-, and unnatural amino acids is reviewed. New opioid compounds have also been identified from peptidomimetic libraries, such as peptoids and alkylated dipeptides, and those identified from acyclic (eg, polyamine, urea) and heterocyclic (eg, bicyclic guanidine) libraries are reviewed.

In Vitro and Direct In Vivo Testing of Mixture-Based Combinatorial Libraries for the Identification of Highly Active and Specific Opiate Ligands

The use of combinatorial libraries for the identification of novel opiate and related ligands in opioid receptor assays is reviewed. Case studies involving opioid assays used to demonstrate the viability of combinatorial libraries are described. The identification of new opioid peptides composed of L-amino acids, D-amino acids, or L-, D-, and unnatural amino acids is reviewed. New opioid compounds have also been identified from peptidomimetic libraries, such as peptoids and alkylated dipeptides, and those identified from acyclic (eg, polyamine, urea) and heterocyclic (eg, bicyclic guanidine) libraries are reviewed.

Parallel Synthesis Technologies in Lead Discovery and Optimization: Strategies and Applications

AbstractFor Abstract see ChemInform Abstract in Full Text.

Knowledge Discovery Applications in High-Throughput Polymer Characterization

AbstractThe use of combinatorial libraries for screening cell-material interactions presents a significant need for robust informatics methods capable of extracting knowledge from large, combinatorial datasets. We describe the development of local quantitative metrics based on distributions of other cells and microstructures about each individual cell. The local metrics are shown to be superior to global, summary statistics in detecting sensitive effects of surface microstructure on proliferation of MC3T3-E1 osteoblasts.

Identification of potential binding sites for the FHA domain of human Chk2 by in vitro binding studies

Human Chk2 is a newly identified tumor suppressor protein involved in signaling pathways in response to DNA damage. The protein consists of a forkhead-associated (FHA) domain and a kinase domain. Identification of binding partners of the Chk2FHA domain is important in understanding the roles of Chk2 in signaling. We report development of an approach involving the use of combinatorial libraries, pull-down assays, surface plasmon resonance (SPR), and nuclear magnetic resonance (NMR) methods to identify possible candidates for the binding sites of Chk2FHA. The approach has been used to identify Thr329 of p53 and Thr1852 of breast cancer type 1 susceptibility protein (BRCA1) as very likely biological binding sites of Chk2FHA. The results provide useful leads for further biological analyses of cell signaling involving the FHA domain of Chk2 protein.

Exploring immunological specificity using synthetic peptide combinatorial libraries

The definition of epitopes for human B and T cells is fundamental for the understanding of the immune response mechanism and its role in the prevention and cause of human disease. This understanding can be applied to the design of diagnostics and synthetic vaccines. In recent years, the understanding of the specificity of B and T cells has been advanced significantly by the development and use of combinatorial libraries made up of thousands to millions of synthetic peptides. The use of this approach has had four major effects: first, the definition of high affinity ligands both for T cells and antibodies; second, the application of alternative means for identifying immunologically relevant peptides for use as potential preventive and therapeutic vaccines; third, a new appreciation of the requirements for TCR interactions with peptide-MHC complexes in immunogenicity; fourth, the establishment of new principles regarding the level of cross-reactivity in immunological recognition.

New opioid peptides, peptidomimetics, and heterocyclic compounds from combinatorial libraries

Abstract: Here we review the use of combinatorial libraries in opioid receptor assays. Following a brief description of the history of the combinatorial field, methods for the generation of synthetic libraries and the deconvolution of mixture-based libraries are presented. Case studies involving opioid assays used to demonstrate the viability of combinatorial libraries are described. The identification of new opioid peptides from combinatorial libraries is reviewed. The peptides found are composed of L-amino acids, D-amino acids, or L-, D-, and unnatural amino acids, and range from tetrapeptides to decapeptides. Likewise, new opioid compounds identified from peptidomimetic libraries, such as peptoids and alkylated dipeptides, and those identified from acyclic (e.g., polyamine, urea) and heterocyclic (e.g., bicyclic guanidine) libraries, are reviewed. © 2000 John Wiley & Sons, Inc. Biopoly 51: 379–390, 1999

New opioid peptides, peptidomimetics, and heterocyclic compounds from combinatorial libraries.

Here we review the use of combinatorial libraries in opioid receptor assays. Following a brief description of the history of the combinatorial field, methods for the generation of synthetic libraries and the deconvolution of mixture-based libraries are presented. Case studies involving opioid assays used to demonstrate the viability of combinatorial libraries are described. The identification of new opioid peptides from combinatorial libraries is reviewed. The peptides found are composed of L-amino acids, D-amino acids, or L-, D-, and unnatural amino acids, and range from tetrapeptides to decapeptides. Likewise, new opioid compounds identified from peptidomimetic libraries, such as peptoids and alkylated dipeptides, and those identified from acyclic (e.g., polyamine, urea) and heterocyclic (e.g., bicyclic guanidine) libraries, are reviewed.

The use of combinatorial libraries to identify ligands that interact with surface receptors in living cells.

AbstractInteractions between combinatorial libraries and various selector proteins, such as antibodies and receptors, have been demonstrated either in solution (1) or while the selector proteins were bound to a solid support (2–5). Before the introduction of the library to a selector protein, the latter is purified in order to avoid nondesirable interactions between various members of the library and nonrelevant contaminants. However, purification of some proteins 1s difficult to achieve, and might be deleterious to then biological activity. It is therefore important to develop methods that employ combinatorial libraries in combination with nonpurified or partially purified selector proteins. In this regard, Jayawickreme and Lerner developed a technique for screening combinatorial libraries employing recombinant receptors expressed in the plasma membrane of transfected melanophors (6,7 and Chapters 13,14). Their technique is based on the biological activity of the expressed receptors and it enables the selection of library members with agonistic or antagonistic activities.KeywordsParental CellPeptide LibraryTissue Culture CellPhage ClonePhage LibraryThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

5-Hydroxytryptophan as a building block in oligopeptides using Fmoc/tBu SPPS

One of the initial steps in the development of therapeutic agents is the identification of lead compounds that bind to the target of interest. Use of combinatorial libraries allows the screening of thousands to millions of compounds. To optimize the characteristics of the first generation of compounds, many of their analogues need to be synthesized. In this sense, 5-hydroxytryptophan closely resembles tryptophan. Both, however, are sensitive to oxidation and alkylation during solid-phase peptide synthesis. In an effort to overcome these side reactions during oligopeptide synthesis, we prepared N α-Fmoc-N in-Boc-5-O-benzyl-5-hydroxytryptophan. To evaluate its properties, this building block was incorporated in a pentagastrin analogue using Fmoc/tBu chemistry. After deprotection and cleavage from the support, the products were purified and identified. The fully deprotected peptide was the main compound, contaminated by its 5-O-benzylated analogue. The relative amount of the latter decreased using longer deprotection times.