Synthesis of novel ceramide-like penetration enhancers

Ceramide-like penetration enhancers have been synthesized by isosteric replacements of the 1-hydroxymethyl and amide moieties of natural ceramides. Metabolically more stable oxime and five-membered heterocyclic (1,2,4-oxadiazole, 1,2,4-triazole, tetrazole) analogues are more polar and possess H-bond acceptor properties, which make them potentially useful in optimizing key intermolecular features in interactions between the modified ceramide structures and the lipid layers of stratum corneum.     

Diversification of a Novel α-Galactosyl Ceramide Hotspot Boosts the Adjuvant Properties in Parenteral and Mucosal Vaccines

The development of potent adjuvants is an important step for improving the performance of subunit vaccines. CD1d agonists, such as the prototypical α-galactosyl ceramide (α-GalCer), are of special interest due to their ability to activate iNKT cells and trigger rapid dendritic cell maturation and B-cell activation. Herein, we introduce a novel derivatization hotspot at the α-GalCer skeleton, namely the N-substituent at the amide bond. The multicomponent diversification of this previously unexplored glycolipid chemotype space permitted the introduction of a variety of extra functionalities that can either potentiate the adjuvant properties or serve as handles for further conjugation to antigens toward the development of self-adjuvanting vaccines. This strategy led to the discovery of compounds eliciting enhanced antigen-specific T cell stimulation and a higher antibody response when delivered by either the parenteral or the mucosal route, as compared to a known potent CD1d agonist. Notably, various functionalized α-GalCer analogues showed a more potent adjuvant effect after intranasal immunization than a PEGylated α-GalCer analogue previously optimized for this purpose. Ultimately, this work could open multiple avenues of opportunity for the use of mucosal vaccines against microbial infections.     

A new ceramide from transgenic crown galls of Panax quinquefolium

A new ceramide(1) was isolated from transgenic crown galls of Panax quinquefolium.The structure was elucidated as(2S,3S, 4R,20E)-2-[(2′R)-2′-hydroxylpalmitoylamino]- 20- hexacosene- 1,3,4-triol on the basis of spectroscopic and chemical methods.     

Ceramide-enriched microdomains in planar membranes

Ceramide has a large effect on the properties of biological membranes, increasing lipid order and promoting lateral phase separation, and plays an important role in cell signaling. This review provides an overview of recent studies of the effects of direct ceramide incorporation and enzymatic ceramide generation on planar supported membranes, including lipid monolayers and supported lipid bilayers. Recent studies have focused on understanding the nucleation, growth and morphology of ceramide gel domains, characterizing the properties of ceramide-rich membrane phases and investigating the effects of ceramide on phase-separated membranes with co-existing liquid-ordered and fluid phases, as models for cellular membranes.     

An Improved Synthesis of Ceramide for Constructing α‐Galactosyl Ceramide Analogs

In spite of numerous synthetic routes to ceramide analogs, relatively few reports of the direct coupling of the unprotected phytosphingosine with the activated palmitic acid via amide bond formation are available. After purification by HPLC, the chromatogram indicated some impurities had not been removed during previous column chromatography. With the pure ceramides in hand, derivatization with the amino group for constructing libraries could be realized.