Cationic antimicrobial peptides (CAPs) are an important component of the innate immune system and are instrumental in the elimination of bacteria, viruses, protozoa, yeast, fungi and cancerous cells from the body. CAPs are comprised of less than 100 amino acids and have a net positive charge due to a multitude of basic residues in their primary sequences. CAPs exert their antimicrobial activity primarily through the formation of pores in microbial membranes, but also play important immunostimulatory roles in the body. Glycosaminoglycans (GAGs) are negatively charged, polydisperse linear polysaccharides found at cellular surfaces. Although many protein-binding interactions of the GAG family, including heparin and heparan sulfate, have been well-characterized, it is not known to what extent endogenous GAGs affect the innate immune system. In the studies here the modulatory activities of GAGs and other polyanionic polysaccharides (PPSs) on CAPs were probed. Initial studies focused on interactions between a short peptide derived from bovine lactoferricin and GAGs. GAGs and other PPSs were then tested for their ability to modulate the antimicrobial activities of a number of CAPs against Gram-positive and -negative organisms. GAGs were also tested for the ability to modulate CAPs binding to bacterial lipopolysaccharide. CAP affinities for the GAGs were determined from lipopolysaccharide competition binding assays. Finally GAGs were evaluated for the ability to protect CAPs from proteolytic degradation. The modulatory activities of GAGs and other PPSs are largely dependent upon all components of the test system and, to a lesser extent, the charge of the molecule.

No description available.

No description available.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2009. / Härtill 5 uppsatser.

No description available.

Thesis (Ph.D.). / Written for the Dept. of Medicine, Division of Experimental Medicine. Title from title page of PDF (viewed 2008/05/08). Includes bibliographical references.

Various additions are used in rubber compounds to accelerate mixing with particulate fillers and to improve behaviour in subsequent processing operations. Cationic surfactants of general structure [RNH2(CH2)3NH3]2+ 2[R'COO] can be used in rubber processing as multifunctional additives (MFA) which act as processing aids, accelerators and mould releasing agents. However, with all these beneficial properties an adverse effect of decreased scorch time was observed when N–tallow–1,3 diaminopropane dioleate (EN444) was used in the filled natural rubber compound.

Several compounds possessing diverse chemical structures have been shown to inhibit the action of protein kinase C (PKC). A general property of some of these compounds is that they inhibit bilayer to hexagonal phase interconversion in phosphatidylethanolamine bilayers. In addition, a large number of PKC inhibitors are positively charged. To clarify the relationship between charge and enzyme inhibition, the effect of the cationic amphiphile sphingosine was studied at different pH's. Inhibition by sphingosine was found to be pH dependent. Above pH 7.75, sphingosine has little or no inhibitory effect. In fact, at pH 8.5 sphingosine slightly enhances enzyme activity above that which occurs when the enzyme is stimulated by diacylglycerol and phosphatidylserine. After correcting for electrostatic repulsion, the intrinsic pK for sphingosine in Triton micelles is 8.5. Inhibition of PKC by sphingosine at physiological pH's therefore correlates with the presence of positive charge. In an attempt to optimize the structural features necessary for inhibition of PKC, a number of compounds which incorporate both positive charge as well as bilayer stabilizing ability were designed. These compounds possess a hydrophobic backbone which does not perturb hydrocarbon packing and have a tertiary or quaternary nitrogen functionality in the head group. All designed amphiphiles inhibit PKC activity; the potency of the amphiphile correlates with the presence of positive charge. Quaternary ammonium bilayer stabilizers are 10 fold more potent than their tertiary amine precursors, generally inhibiting in the 10 - 60 (mu)M range using the Triton mixed micelle assay. Aside from charge, factors such as the structure of the amine containing head group and its length from the hydrocarbon moiety did not markedly influence inhibitor potency. In contrast, the hydrocarbon backbone did influence potency. Cationic amphiphiles containing asteroid backbone were more potent than their straight chain analogues. These amphiphiles do not appear to alter the partitioning of PKC from the aqueous phase to the membrane surface. A number of bilayer stabilizing compounds possessing carboxylate and sulfate anions in addition to the quaternary nitrogen functionality were also designed. Although inhibitor potency correlated with the amount of charge present on the amphiphile, charge could not account for all the observed effects. Changes in the position of the charged functionalities and hydrocarbon length resulted in marked differences in amphiphile potency. Some inhibited in the submicromolar range. The results of these studies suggest that a combination of positive charge and a bilayer stabilizing structural characterisitic provides a basis for the rational design of PKC inhibitors. / Thesis / Master of Science (MS)

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.