Lipidization strategies

Scheme 1 Anionic PEG-lipid strategy. Abbreviation PEG, poly(ethylene glycol).

While X in increases with lipophilicity, AUC decreases due to higher uptake across all cell membranes including those of peripheral tissues. Therefore limits are imposed on the gain in brain delivery by the lipidization strategy. In fact, for azidothymidine lipidization with the lipophilic adamantane moiety, CSF concentrations decreased by a factor of 10 as a result of a decrease in AUC [54]. 

Increasing the lipid character of a hydrophilic drag molecule may enhance its membrane-penetrative properties and thus improve oral bioavailability. In particular, lipidization strategies have been investigated for the oral absorption of therapeutic peptides and proteins, which are generally hydrophilic compounds. 

The problems with the various lipidization strategies described include the limitations posed by the 400-600 Dalton molecular weight threshold of the BBB. Increased lipidization will also cause enhanced dmg distribution into peripheral tissues, thereby offsetting the enhanced BBB permeability effects, and active concentrations in the CNS can only be maintained if the blood concentrations are maintained at adequately high levels. 

Mori et al. have demonstrated the most dramatic uses of lithiated epoxides in natural product synthesis [62]. By employing the chemistry developed by Jackson, and subsequently performing a Lewis acid-catalyzed (BF3 OEt2) cyclisation, tetra-hydrofuran, tetrahydropyran, and oxepane rings are readily accessed this strategy is demonstrated by the synthesis of the marine epoxy lipid 173 (Scheme 5.40) [63]. 

In this chapter we will examine how cells and enzymes are used in the transformation of lipids. The lipids are, of course, a very diverse and complex series of molecular entities including fatty acids, triglycerides, phospholipids, glycolipids, aliphatic alcohols, waxes, terpenes and steroids. It is usual to teach about these molecules, in a biochemical context, in more or less the order given above, since this represents a logical sequence leading from simple molecules to the more complex. Here, however, we have adopted a different strategy. 

Schmitz G, Liebisch G, Langmann T (2006) Lipidomic strategies to study structural and functional defects of ABC-transpoiters in cellular lipid tr afficking. FEBS Lett 9 5 80(23) 5597-610. Review... 

Direct evidence for the biodegradation of benzene and toluene in a contaminated aquifer was lacking, and an alternative strategy was examined. Bio-Sep beads were maintained in tubes and [ C] benzene or [ C]toluene were sorbed on to the surface. Analysis of 8 C in fatty acids extracted from lipids showed enrichments up to 13,500 ppm for benzene and... 

Normally, the cascade from oxygen to water is well controlled by SOD, catalase and endogenous antioxidants such as glutathione, ascorbate and vitamin E. Vitamin E is the most important membrane-bound antioxidant. However, during ischaemia, the local control of ROS is lost, thus reactive free radicals can attack the membranes and lipid peroxidation begins. Endogenous antioxidants can be supplemented. This section describes this supplementation strategy. 

The development of CHD is a lifelong process. Except in rare cases of severely elevated serum cholesterol levels, years of poor dietary habits, sedentary lifestyle, and life-habit risk factors (e.g., smoking and obesity) contribute to the development of atherosclerosis.3 Unfortunately, many individuals at risk for CHD do not receive lipid-lowering therapy or are not optimally treated. This chapter will help identify individuals at risk, assess treatment goals based on the level of CHD risk, and implement optimal treatment strategies and monitoring plans. 

Jones, J. J. Stump, M. J. Fleming, R. C. Lay, J. O. Wilkins, C. L. Strategies and data analysis techniques for lipid and phospholipid chemistry elucidation by intact cell MALDI-FTMS. /. Am. Soc. Mass Spectrom. 2004,15,1665-1674. 

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