Convergent synthetic methodology for the construction of self-adjuvanting lipopeptide vaccines using a novel carbohydrate scaffold

A novel convergent synthetic strategy for the construction of multicomponent self-adjuvanting lipopeptide vaccines was developed. A tetraalkyne-functionalized glucose derivative and lipidated Fmoc-lysine were prepared by novel efficient and convenient syntheses. The carbohydrate building block was coupled to the self-adjuvanting lipidic moiety (three lipidated Fmoc-lysines) on solid support. Four copies of a group A streptococcal B cell epitope (J8) were then conjugated to the glyco-lipopeptide using a copper-catalyzed cycloaddition reaction. The approach was elaborated by the preparation of a second vaccine candidate which incorporated an additional promiscuous T-helper epitope

α-Galactosidases and their applications in biotransformations

α-d-Galactosidases (α-d-galactoside galactohydrolase, E.C. 3.2.1.22) are exoglycosidases, which in vivo catalyze the hydrolysis of simple and complex oligo- and polysaccharides containing terminal α-d-galactosyl groups. A number of industrial applications of α-d-galactosidases are known, mainly in the sugar industry, pulp and paper industry or medicine. Although α-d-galactosidases occur in all living systems, microbial and possibly plant enzymes are preferred for practical applications. The regioselectivity of glycosidases is somewhat poor. Selective protection of oligosaccharides and development of new modified donors/acceptors is a promising method to overcome this problem. Genetic engineering has enabled the creation of glycosynthases from the hydrolytic glycosidases, which are highly complementary to glycosyltransferases. The present review summarizes recent advances in the application of α-d-galactosidases in synthetic and biotransformation applications

Development and characterization of anionic liposaccharides for enhanced oral drug delivery

The aim of this study was to synthesize charged amphoteric molecules, which after complexation with poorly bioavailable drugs would have the potential to improve their oral uptake. Novel anionic liposaccharide derivatives containing D-glucose and lipoamino acids were synthesized by solution phase peptide synthesis. High sensitivity isothermal titration microcalorimetry was used to determine the critical aggregation concentration and the thermodynamic profiles. Hemolytic and cytotoxic activities of the liposaccharides were studied and they revealed that the liposaccharides were non-toxic at the concentration used for oral administration. Mixing a model drug, tobramycin, with the liposaccharide containing two lipids formed aggregates around 200 nm, which increased tobramycin partitioning between noctanol/water. The results suggested that the studied liposaccharide with two lipids was safe to apply biologically and may have an absorption enhancing activity on hydrophilic, orally poorly available drugs. (C) 2012 Elsevier B. V. All rights reserved

Carbohydrates in vaccine development

Despite advances in the development of new vaccines, there are still some diseases with no vaccine solutions. Therefore, further efforts are required to more comprehensively discern the different antigenic components of these microorganisms on a molecular level. This review summarizes advancement in the development of new carbohydrate-based vaccines. Following traditional vaccine counterparts, the carbohydrate-based vaccines introduced a new approach in fighting infectious diseases. Carbohydrates have played various roles in the development of carbohydrate-based vaccines, which are described in this review, including carbohydrates acting as antigens, carriers or targeting moieties. Carbohydrate-based vaccines against infectious diseases, such as group A streptococcus, meningococcal meningitis and human immunodeficiency virus, are also discussed. A number of carbohydrate-based vaccines, such as Pneumovax 23, Menveo and Pentacel, have been successfully marketed in the past few years and there is a promising standpoint for many more to come in the near future