Combinatorial Chemistry & High Throughput Screening - Volume 5, Issue 7, 2002

During the last 12 years, antibody combinatorial libraries have provided a new approach for the construction and production of reagents and drugs based on the human monoclonal antibodies. Studies employing antibodies or antibody mimics have become an important part of the explosive growth of proteomics. This places tremendous emphasis on the new approaches for faster library screening, improved methods of selec Read More

We outline a joint academic / industrial (CNRS / AVENTIS) functional genomics project aiming at the discovery of new anti-bacterial gene targets. Starting from all publicly available bacterial genomes, a subset of the most evolutionary conserved protein-coding genes has been identified. We retained genes with clear homolog in E. coli and at least one gram-positive bacterium among B.subtilis, M. tuberculosis, L. lactis or S. py Read More

Flow-injection NMR is a very attractive technique for identifying weak but specific ligandmacromolecule interactions. The low-sensitivity of this method is, however, a major concern which hinders its widespread application to large-scale screening. Focussing on RNA-targeting ligands, we have shown in this report that it is possible to design a peptide library that will simultaneously satisfy a number of physicochemical restr Read More

This paper describes the applications which are used to automate the analysis of encoded combinatorial libraries. Commercial packages from MDL, Oracle and Agilent are linked with application software written in C / C++, in Microsoft Access and in ChemStation macro language. Encoding correspondence lists for each of up to three synthetic steps are conveniently associated with building block lists using the first applicatio Read More

A library of 72 compounds related to N- [4-(benzyloxy) benzoyl]alanine (I) was synthesized, prepared and screened for α-glucosidase inhibitory activity. Four compounds showed potent inhibition, six compounds moderate inhibition, and 16 were weak inhibitors. One compound, N- [4-(benzyloxy) benzoyl] serine, was found to be a potent inhibitor of α-glucosidase with 100% inhibition at 1μM. This inhibitor was at least fi Read More

Peptides that consist of 19 residues with random sequences (X19) were considered to deliver antigenic stimuli to CD4T cells. When IL-4, IL-7, IL-9, IL-15 and agonistic Ab to CD29 were co-cultured with single peripheral CD4T cells in the presence of X19 and feeder cells, T cells exhibited clonal expansion. These T cell clones showed heterogeneous proliferation patterns against KGXXXXXXXXXGK-based and KGXXXXXXXXXGKGKK Read More

A simple and fast one-pot method using microwave irradiation for the synthesis of a number of small libraries of diverse heterocycles is described in this paper. The two-step one-pot method includes the formation of alkylaminopropenones or alkylaminopropenoates in 5 min at 180 °C and a subsequent treatment with dinucleophiles for 3 to 5 min at 150 °C to 180 °C to form a variety of biologically interesting heterocycles in a Read More

A general procedure for the synthesis of a large variety of compounds comprising an α, β-unsaturated carbonyl functionality was developed. The use of one-pot cascade synthesis with (triphenylphosphora-nylidene)ethenone as a versatile reagent for various formations including heterocycles of different ring sizes and unsaturated amides in combination with microwave dielectric heating is described. The method was used to s Read More

Aqueous solubility is a critical physicochemical property and must be addressed early during drug discovery research. Due to the difficulty in accurately predicting aqueous solubility in silico, high throughput experimental determination of aqueous solubility is in great demand. This study evaluates a method using a multi-wavelength UV plate reader and disposable 96-well UV plates for fast solubility determination. It was d Read More