EXAFS study of liposome-encapsulated cisplatin

The anticancer agent cisplatin encapsulated in sterically stabilized liposomes is studied with extended X-ray absorption fine structure (EXAFS) method. Analysis of local atomic structure around Pt atoms clearly indicates that the liposome-encapsulated drug is chemically stable and does not hydrolyze. Cisplatin forms a supersaturated solution in the liposome interior at a concentration about eight-fold above its aqueous solubility.     

Microencapsulation of DNA Within alginate microspheres and crosslinked chitosan membranes for in vivo application

Calf thymus DNA was microencapsulated within crosslinked chitosan membranes, or immobilized within chitosan-coated alginate microspheres. Microcapsules were prepared by interfacial polymerization of chitosan, and alginate microspheres formed by emulsification/ internal gelation. Diameters ranged from 20 to 500 Μm, depending on the formulation conditions. Encapsulated DNA was quantifiedin situ by direct spectrophotometry (260 nm) and ethidium bromide fluorimetry, and compared to DNA measurements on the fractions following disruption and dissolution of the microspheres. Approximately 84% of the DNA was released upon core dissolution and membrane disruption, with 12% membrane bound. The yield of encapsulation was 96%. Leakage of DNA from intact microspheres/capsules was not observed. DNA microcapsules and microspheres were recovered intact from rat feces following gavage and gastrointestinal transit. Higher recoveries (60%) and reduced shrinkage during transit were obtained with the alginate microspheres. DNA was recovered and purified from the microcapsules and microspheres by chromatography and differential precipitation with ethanol. This is the first report of microcapsules or microspheres containing biologically active material (DNA) being passed through the gastrointestinal tract, with the potential for substantial recovery.     

Glycosyl azide—a novel substrate for enzymatic transglycosylations

Glycosyl azides are new efficient donors for glycosidases. Their high water solubility facilitates transglycosylations with comparable or better yields than common O-glycosides. The azido group totally changes the β-GalNAc-ase/β-GlcNAc-ase ratio in β-N-acetylhexosaminidases (from the usual 0.3-1.0 to <0.01), contrary to all known aglycons.     

General Aspects and Optimization of Enantioselective Biocatalysis in Organic Solvents: The Use of Lipases [New Synthetic Methods (76)]

Enantioselective biocatalysis in nonaqueous media is becoming increasingly important in preparative synthetic chemistry. This article discusses (1) the general catalytic properties of enzymes in nonaqueous environments, (2) the basic principles that govern lipase-catalyzed enantioselective esterification and transesterification reactions in organic media for the preparation of optically active acids and alcohols, (3) the determination of kinetic and thermodynamic parameters, and (4) the quantitative analysis of published data.     

Current methods for site-directed structure generation

Summary There has been a rapid growth of interest in techniques for site-directed drug design, fuelled by the increasing availability of structural models of proteins of therapeutic importance, and by studies reported in the literature showing that potent chemical leads can be obtained by these techniques. Structure generation programs offer the prospect of discovering highly original lead structures from novel chemical families. Due to the fact that this technique is more-or-less still in its infancy, there are no case studies available that demonstrate the use of structure generation programs for site-directed drug design. Such programs were first proposed in 1986, and became commercially available in early 1992. They have shown their ability to reproduce, or suggest reasonable alternatives for, ligands in well-defined binding sites. This brief review will discuss the recent advances that have been made in the field of site-directed structure generation.     

Inhibitors of biotin biosynthesis as potential herbicides

Isosteric derivatives and analogues of the 7-keto-8-aminopelargonic acid (KAPA), 7,8-diaminopelargonic acid (DAPA) and desthiobiotin (DTB) vitamer intermediates involved in the biosynthetic pathway of biotin were prepared and evaluated as potential herbicides. The most active compound was desmethyl-KAPA which displayed a GR₅₀ (concentration of the active compound that causes a 50% growth inhibition) value of 8 ppm, where values <50 ppm are considered herbicidal. Other KAPA analogs where the terminal Me group was replaced by bulkier substituents such as Et, i-Pr and HOCH₂ showed moderate activity.