ABSTRACT
Se presenta un documento de opinión elaborado por la sección de Medicinal Chemistry de IUPAC, que cuenta además con el acuerdo de un buen número de científicos, algunos de los cuales figuran al final del trabajo. Se plantea el papel que puede tener el descubrimiento de medicamentos en el desarrollo de las sociedades y mantenimiento de la biodiversidad en base a los trabajos en productos naturales. Se plantean recomendaciones de aplicación en los países que están en la búsqueda de su desarrollo científico y tecnológico en el medicamento. Es intención de la sección de Medicinal Chemistry de IUPAC su difusión internacional, por lo que agradecen la colaboración de las sociedades científicas de los diferentes países (AU)
Subject(s)
Humans , Societies, Scientific , Chemistry, Pharmaceutical , Ecosystem , Biological FactorsABSTRACT
This document has been elaborated by the IUPAC Medicinal Chemistry section and is backed by a large number of scientists, many of whom have had direct involvement and whose names appear at the end of the article. This work discusses the role that the discovery of new medicinal agents has in the development of societies as well as in the conservation of biodiversity in terms of work carried out on natural products. Also included are several recommendations for countries which are presently in search of their own scientific and technological development in medicinal agents. The IUPAC Medicinal Chemistry section would appreciate the collaboration of the scientific societies in every country to aid in the diffusion of this document.
Subject(s)
Biological Products , Chemistry, Pharmaceutical , Social Change , Conservation of Natural Resources , Species SpecificityABSTRACT
The peptidyl-tRNA analogue N-(chloroacetyl)phenylalanyl-tRNAPhe was prepared by chemical aminoacylation and prebound to the P site of Escherichia coli ribosomes in response to poly(uridylic acid). Admixture of phenylalanyl-tRNAPhe to the A site resulted in the formation of two "dipeptides", one of which was formed by displacement of chloride ion from the peptidyl-tRNA. This constitutes the first example of ribosome-mediated formation of a peptide of altered connectivity and suggests a need for revision of the current model of peptide bond formation. Also suggested by the present finding is the feasibility of utilizing tRNAs to prepare polypeptides of altered connectivity in an in vitro protein biosynthesizing system.
Subject(s)
Escherichia coli/metabolism , RNA, Transfer, Amino Acyl/metabolism , Ribosomes/metabolism , Chloramphenicol/pharmacology , Peptidyl Transferases/metabolism , Ribosomes/drug effectsABSTRACT
T4 RNA ligase was employed for the condensation of Escherichia coli tRNAPhe missing cytidine-75 and adenosine-76 (tRNAPhe-COH; the acceptor "oligomer") with each of several chemically acylated derivatives of pCpA (the donor "oligomer"). The resulting "chemically misacylated " tRNAPheS were obtained in 20-65% yields following chromatographic workup on DEAE-cellulose and benzoylated DEAE-cellulose. Characterization of the chemically misacylated tRNAs was accomplished by (i) enzymatic reaminoacylation of chemically misacylated tRNAPhe with phenylalanine by E. coli phenylalanyl-tRNA synthetase following chemical deacylation of the "incorrect" amino acid, (ii) comparison of the hydrolytic effects of Cu2+ solutions on chemically and enzymatically prepared samples of N-acetyl-L-phenylalanyl- tRNAPheS , and (iii) measurement of the chromatographic behavior of the tRNA species derived from chemical misacylation .
