ABSTRACT
The technique of quantitative structure-activity relationships (QSAR) is well accepted by the drug design community. The analogous technique of quantitative structure-property relationships (QSPR) has applications in the field of polymer chemistry. A variety of molecular modeling and molecular orbital techniques was used to find molecular descriptors that could be used to derive an empirical equation to describe the glass transition temperature of two related classes of poly(arylene ether)s. The derived equation was then used to predict the thermal characteristics of another polymer of the same type.
Subject(s)
Computer Graphics , Models, Molecular , Polymers/chemistry , Computer Simulation , Models, Chemical , Molecular Structure , Plastics/chemistry , Polymers/pharmacology , Structure-Activity RelationshipABSTRACT
A model of angiogenin has been prepared by homology modelling, based upon the structure of ribonuclease A. This model has been used to postulate an inhibitor based upon the angiostatic agent TAN1120. The complex of ribonuclease A with a dinucleotide has been modelled and used as a guide to the binding orientation of daunomycin--the closest TAN1120 analogue for which the crystal structure and stereochemistry are available.
Subject(s)
Anthracyclines , Drug Design , Proteins/antagonists & inhibitors , Animals , Antibiotics, Antineoplastic/chemistry , Binding Sites , Cattle , Computer Simulation , Daunorubicin/chemistry , Humans , Models, Molecular , Molecular Structure , Proteins/chemistry , Ribonuclease, Pancreatic/chemistry , Stereoisomerism , ThermodynamicsABSTRACT
The possible role of the gamma-glutamyl cycle in the transport of amino acids, using the Caco-2 cell monolayer as an in vitro model of the small intestine, has been investigated. The transport of [2-3H]glycine and [2-3H]glycylglycine through the Caco-2 monolayer has been shown to occur by two modes of action. Active transport is unidirectional from apical to basolateral region and is a carrier mediated system. The enzyme gamma-glutamyl transpeptidase seems to be involved in this process, since when the enzyme is inhibited, the active transport is also inhibited. However transport still takes place, and this occurs by a slower non-active process, which is bidirectional and is mediated by passive diffusion. The rate of transport of [2-3H]glycylglycine and [2-3H]glycine were 585 (+/- 24) and 287 (+/- 16) pmolcm-2min-1 respectively, while the non-active transport takes place at 87 (+/- 6) pmolcm-2min-1. Thus, amino acid translocation in Caco-2 cells is shown to occur by two methods, one of which involves the gamma-glutamyl cycle.
