If you are experiencing problems downloading PDF or HTML fulltext, our helpdesk recommend clearing your browser cache and trying again. If you need help in clearing your cache, please click here . Still need help? Email help@ingentaconnect.com

Interaction of Proteins with Lipid Rafts Through Glycolipid-Binding Domains:Biochemical Background and Potential Therapeutic Applications

$63.10 plus tax (Refund Policy)

Buy Article:

Abstract:

The wide biochemical diversity of glycolipids in membranes explains why these molecules are often selected by pathogens (viruses, bacteria, prions) as primary sites of interactions with the cell surface. Moreover, glycolipids concentrate into cholesterol/ glycolipid-rich microdomains where they can reach high local concentrations consistent with the multivalent attachment of pathogens on the cell surface. Finally, recent studies have shown that glycolipids could also modulate protein conformation. This chaperone activity of glycolipids has been associated with various pathogenic processes including HIV infection, prion propagation, and amyloid aggregation in Alzheimer's and Creutzfeldt-Jakob's diseases. Despite the potential interest for drugs mimicking glycolipid structure and function, the physicochemical properties of authentic glycolipids suggested that it might be difficult to obtain synthetic glycolipid analogues able to neutralise those pathogens before they could reach the cell surface. Recent data obtained with mono-, di-, and trihexosylceramide (GalCer, LacCer and Gb3) have proven that this was absolutely not the case and that highly active inhibitors could be designed through slight modifications of glycolipid structure. Biochemical studies of glycolipid-protein interactions have highlighted the importance of CH- π stacking interactions between galactosyl head groups of the glycolipid and aromatic amino acids of the protein. The discovery of this unique mechanism of interaction may allow a rational strategy for the design and synthesis of glycolipid-based molecules as new anti-infectious and/or anti-amyloidogenesis compounds. This strategy, which takes into account the hierarchical organisation of glycolipids into discrete membrane microdomains as well as their association with cholesterol, is discussed in the present review.

Keywords: Creutzfeldt-Jakob diseases; GalCer; conformation; glycolipid-binding domain; sphingolipids

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986707782360033

Affiliations: Universite Paul Cezanne, Laboratoire des Interactions Moleculaires et Systemes Membranaires, Faculte des Sciences et Techniques de Saint-Jerome, Service 331, 13397 Marseille Cedex 20, France.

Publication date: November 1, 2007

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
Related content

Tools

Favourites

Share Content

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
X
Cookie Policy
ingentaconnect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more