Synthetic lipid A analogue

Figure 4. Biological activities of synthetic lipid A analogues. The designations of the preparations are as in Chapter 11.

Brandenburg, K., Kusumoto, S., Seydel U. Conformational studies of synthetic lipid A analogues and partial structures by infrared spectroscopy. Biochim Biophys Acta 1329 (1997) 193-201. 

Synthetic lipid A analogues were used in FTTR investigations to study possible intermolecular conformations of neighboring molecules [79]. There is good evidence that the bisphosphory-lated /3-(l—>6)-linked GlcN disaccharide backbone of lipid A is inclined (20—40° relative to the membrane normal), thus, the phosphate linked to 01 is reaching to the outside and that at 04 is buried in the membrane. This model is supported by data from transition temperature measurements and calorimetric experiments. However, it should be noted that other authors reported the reverse conformation with the 04 phosphate on the surface and the 01 phosphate in the membrane [80,81]. 

Lipid A Analogues. - Of a set of eleven new JV-acylated L-serine-containing 2-amino-2-deoxy-D-glucose derivatives synthesized as Lipid A analogues and evaluated as synthetic immunoadjuvants, compound 78 had the greatest... 

Despite these uncertainties several laboratories have now started to chemically synthesize lipid A substructures and analogues (32). These preparations are presently being compared with (nativeT free lipid A by physicochemical methods of analysis, and are being tested in a variety of biological systems (33). It is obvious that these synthetic samples will be of great significance in the verification of the structural proposals made for lipid A. 

Tsujimoto, M., Kotani, S., Okunaga, T., Kubo, T., Takada, H., Kubo, T., Shiba, T., Kusumoto, S., Takahashi, T., Goto, Y. Enhancement of humoral immune responses against viral vaccines by a non-pyrogenic 6-O-acylmuramyldipeptide and synthetic low toxicity analogues of lipid A. 

Lipid A, its relatives lipid X and Y, and their analogues are esterified 2-amlno-2-deoxy-D-glucopyranose derivatives, as exemplified by the recently synthesized Proteus mirabilis lipid A (83). Novel synthetic aspects generally involve protecting group manipulations and carboxylic and phosphoric ester forming procedures further details may be found in Chapter 7. The majority of publications have come from the groups of Achlwa (mostly full... 

The study of liposomes as dmg-delivery agents has been ongoing for decades. The lipids for liposome formation are typically harvested by extraction from egg yolks and soybeans, and a number of recipes exist for generating liposomes of various diameters. Because the shell material in liposomes is not polymeric, we will not discuss them in depth, limiting ourselves only to those aspects that are pertinent to synthetic analogues like the copolymer vesicles of the next section. 

The current review is of necessity selective. Over the two year period covered, there has been impressive advances in several areas of P(V) chemistry. For example, biological aspects of quinquevalent phosphorus acids chemistry continue to increase in importance. A wide variety of natural and unnatural phosphates including inositols, lipids, some carbohydrates and their phospho-nates, phosphinates and fluorinated analogues has been synthesized. Special attention has been paid to the synthesis of phosphorus analogues of all types of amino acids and some peptides. Numerous investigations of phosphate ester hydrolysis and related reactions continue to be reported. Interest in approaches to easier detoxification of insecticides continues. A number of new and improved stereoselective synthetic procedures have been elaborated. The importance of enantioselective and dynamic kinetic asymmetric transformations is illustrated in many publications. 

Sufentanil, a fentanyl analogue, is a highly lipid-soluble synthetic opioid with high affinity for OP3 (p) opioid receptors and a potency some 5-10 times that of fentanyl. It is a short-acting analgesic. 

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