RESUMO
A model study aiming at exploring the limits of sandwich immunoassays of very small molecules is described. Combinatorial association of antibody couples to detect small molecules constituted by two small epitopes connected via different linear spacers was used to investigate the minimum size of compounds susceptible to be simultaneously bound by two distinct antibodies. The results clearly indicated that despite the fact that below 10 carbon atoms unfavorable interactions between antibodies took place, molecules bearing two epitopes separated by only 5 carbon atoms might be directly detected by sandwich immunoassays.
Assuntos
Imunoensaio/métodos , Anticorpos Monoclonais/imunologia , Epitopos/imunologia , Histidina/imunologia , Ácido Homovanílico/análogos & derivados , Ácido Homovanílico/imunologia , Peso MolecularRESUMO
Many natural privileged scaffolds contain a basic nitrogen atom, which often is a key element of pharmacophore and a chemically reactive centre as well. In our ongoing research program devoted to the design of targeted libraries based on acidic templates, we developed methods to convert privileged basic compounds -like natural alkaloids or drugs into acidic compounds. This conversion led to a profound alteration of the pharmacophore, without changing the overall shape and lipophilicity of the molecule. We expect such modifications to generate unexpected biological activities. Recently, we focused on derivatives of squaric acid, a vinylogous carboxylic acid. Two series were studied. First we describe a new, selective parallel synthesis of squaramic acids from a dissymmetric diester (3-tert-butoxy-4-ethoxy-cyclobut-3-en-1,2-dione). This efficient procedure avoids the synthesis of the undesired squaramides. Secondly we describe a microplate parallel synthesis (15 micromol-scale) of squaric acid hydroxamate amides from a squaric hydroxamate ester.
Assuntos
Técnicas de Química Combinatória/métodos , Ciclobutanos/química , Preparações Farmacêuticas/química , Bibliotecas de Moléculas Pequenas/química , Aminas/síntese química , Aminas/química , Quelantes/síntese química , Quelantes/química , Química Farmacêutica/métodos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Ésteres/química , Ácidos Hidroxâmicos/química , Estrutura Molecular , Preparações Farmacêuticas/síntese química , Piperidinas/química , Bibliotecas de Moléculas Pequenas/síntese química , Zinco/químicaRESUMO
This paper describes the asymmetric version of highly atom-economical alkoxycyclization of 1,6-enynes, using a combination of silver salts with the Pt(II)/(R)-Ph-BINEPINE system.