No description available.

No description available.

No / Methodology for the efficient and facile synthesis of glycosyl disulfides is reported. A one-pot procedure employing mild conditions using diethyl azodicarboxylate is described to synthesise a series of glycosyl disulfides in excellent yields.

Our effort to provide an efficient route to serine glycosides with utility in glycopeptide synthesis has led to the identification of two particularly effective promoters of O-glycosylation. Indium(III) bromide and scandium(III) triflate were shown to be superior promoters of microwave accelerated O-glycosylation utilizing peracetyl carbohydrate donors. 247, 249 These Lewis acids afforded several advantages over previously described promoters including, increased yields, tolerance to moisture, decreased environmental toxicity, ease of work up, and increased reproducibility. Both affected the microwave accelerated glycosylation of Fmoc-ser-OH with sugar peracetates providing superior yields to previously reported methods. For larger scale work the two step route involving the glycosylation of Fmoc-Ser-OBn followed by removal of the benzyl protecting group via hydrogenolysis was preferred. Of the two Lewis acids, the minimally active indium (III) bromide was preferred, as it afforded slightly higher yields and was effective in catalytic quantities. Three groups of helical DAMGO glycopeptide analogs were synthesized in order to provide a better understanding of the structure activity relationships of these opioid peptides. Although the introduction of the amphipathic helix significantly affected binding of the DAMGO message, there was no correlation between binding affinity at the individual opioid receptors and the degree of helicity. In general, addition of the helical address imparted increased affinity for the kappa receptor. The nature of the linker connecting the N-terminal DAMGO sequence and the C-terminal helical address effected binding affinity only slightly. Successive addition of positive charges to the address increased binding at all three opioid receptors until a maximum was reached at a positive two address charge. Although, the amphipathic helix was shown to moderate receptor selectivity, the native mu preference of the DAMGO message was retained Two groups of fluorescent analogs of the mixed δ / μ opioid agonist MD100 were prepared. Within the first series, the fluorescent label was attached to the interior of the address sequence employing the pNZ moiety as a secondary protecting group. The second series of analogs was based on NovaTag™ resin, and allowed for attachment of the fluorophore at the carboxy terminus. The influence on helicity imparted by fluorophore conjugation depended on the nature and point of attachment of the label. The disruption of secondary structure associated with attachment of the fluorescent correlated with decreased binding affinity at the individual opioid receptors. Preliminary in vivo results were encouraging. The least parent like of the MD100 fluorescent analogs was shown to be taken up into endothelial cells. This suggests that the labeled glycopeptides are likely to cross the blood-brain barrier.

No description available.

No description available.

1. Colorimetric Assay for Cyanide and Cyanogenic Glycoside Using Polysorbate 40-Stabilized Gold Nanoparticles. This study described a simple and homogeneous method for the selective and sensitive detection of cyanide and endogenous biological cyanide using polysorbate 40-stabilized gold nanoparticles (PS 40-AuNPs). Neutral PS 40 molecules enable citrate-capped AuNPs to stabilize in a high-salinity solution. The addition of cyanide to a solution of PS 40-AuNPs resulted in the formation of AuCN(s) on the NP surface and Au(CN)2¡V in an aqueous solution. The removal of PS 40 molecules from the NP surface rendered the AuNPs unstable in a high-salinity solution, leading to NP aggregation. The formation of AuCN(s) and Au(CN)2¡V was demonstrated by means of surface-assisted laser desorption/ionization time of flight mass spectrometry and inductively coupled plasma mass spectroscopy, respectively. PS 40-AuNPs were capable of selectively detecting cyanide at concentrations as low as 500 nM. Additionally, the minimum detectable concentration of linamarin (cyanogenic glycoside) was measured to be 1 uM using PS 40-AuNPs. This probe was successfully applied to the determination of cyanide in tap water, the monitor of cyanide removal during food processing, and the quantification of linamarin in cassava root. 2. Colorimetric detoxification and monitored cyanogenic glycoside in plants/fruit using polysorbate 40-stabilized gold nanoparticles. Developing rapid, highly sensitive, and selective detection/inhibition of cyanide/cyanogenic glycoside from plants and foods is extremely essential for human life safety. Here we report a strategy for the colormetric visualization of cyanogenic glycoside using polysorbate 40 stabilized gold nanoparticle (PS 40-AuNPs). Two cyanogenic glycosides (amygdalin and linamarin) were chosen to determine the efficiency of acid hydrolysis. According to US Department and Health and Human Services standard cyanide antidote kit, sodium thiosulfate and hydroxocobalamin (vitamin B12a) seems to be an appropriate antidote for treatment cyanide poisoning victims. The addition of thiosulfate/vitamin B12a to a solution of cyanide/cyanogenic glycosides resulted in the formation of thiocyanate/vitamin B12 in an aqueous solution, which couldn¡¦t etch PS 40-AuNPs and inhibit the aggregation of PS 40-AuNPs in a high-salt solution. The inhibition/detoxification efficiency (IC50) of thiosulfate and vitamin B12a were studied for treatment of cyanide and hydrolyzed cyanogenic glycoside. This probe was also used to monitor the removal of cyanide, estimated the concentration of cyanide and detoxification of cyanide by thiosulfate in plants/fruit sample.

The oligosaccharide domain of many secondary metabolites have been demonstrated to be pivotal for the biological efficacy of the parent glycoconjugate. In most cases, the alteration or removal of these carbohydrate residues results in the greatly diminished or completely abolished biological activity of the natural product. A common structural motif found in secondary metabolites possessing carbohydrate domains is the 2-deoxy-β-glycosidic linkage which are among the most difficult to establish in a stereocontrolled fashion. Chapter I provides background information describing the difficulties associated with the synthesis of 2-deoxy-β-glycosidic linkages in addition to a sampling of the current methodology available for their construction. Chapter II details our use of diethyl and pinacol phosphite glycosyl donors towards a direct synthesis of a designed 2-deoxy-β-oligosaccharide in a "one-pot" process which constitutes a novel approach towards the synthesis of these glycosidic linkages. Lomaiviticin A was isolated as the major metabolite from fermentation of the halophilic strain LL-37I366 which was later assigned the name Micromonospora lomaivitiensis. Lomaiviticin A displayed potent biological activity towards numerous cancer cell lines with IC50 values ranging from 0.01 to 98 ng/ml. While postulated to induce double-stranded DNA cleavage, the mechanism of action was unique when compared to known DNA-damaging agents such as adriamycin and mitomycin C. Chapter III details progress towards the synthesis of lomaiviticinone employing an "inside-out" strategy to take advantage of the molecule's own C2-symmetrical nature. The focus of the chapter will pertain to our efforts to construct the stereochemically-rich cyclohexenone central core highlighted by the use of organometallic C-C bond formation processes.

Thesis (doctoral)--Karolinska Institutet, Stockholm, 1983. / Extra t.p. with thesis statement inserted. Includes the author's four published papers. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (doctoral)--Karolinska Institutet, Stockholm, 1983. / Extra t.p. with thesis statement inserted. Includes the author's four published papers. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.