Synthesis and Convenient Functionalization of Azide-Labeled Diacylglycerol Analogues for Modular Access to Biologically Active Lipid Probes
| Autor: | Michael D. Best, Denghuang Gong, Matthew D. Smith, Justin C. Reno, Christopher G. Sudhahar, Robert V. Stahelin |
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| Rok vydání: | 2008 |
| Předmět: |
Azides
Biomedical Engineering Pharmaceutical Science Bioengineering Diglycerides Membrane Lipids chemistry.chemical_compound Glycolipid Binding site Protein kinase A Receptor Phospholipids Diacylglycerol kinase Pharmacology Binding Sites Chemistry Organic Chemistry Peripheral membrane protein Affinity Labels Surface Plasmon Resonance Membrane Biochemistry lipids (amino acids peptides and proteins) Azide Glycolipids Biotechnology |
| Zdroj: | Bioconjugate Chemistry. 19:1855-1863 |
| ISSN: | 1520-4812 1043-1802 |
| DOI: | 10.1021/bc8001002 |
| Popis: | Cell membrane lipids have been identified as key participants in cell signaling activities. One important role is their involvement as site-specific ligands in protein-membrane binding interactions, which result in the anchoring of peripheral proteins onto cellular membranes. These events generally regulate protein function and localization and have been implicated in both normal physiological processes and those pertaining to disease state onset. Thus, it is important to elucidate the details of interactions at the molecular level, such as lipid-binding specificities and affinities, the location of receptor binding domains and multivalency in binding. For this purpose, we have designed and developed azido-tagged lipid analogues as conveniently functionalizable lipid probe scaffolds. Herein, we report the design and synthesis of the initial structure of this type, diacylglycerol analogue 2, which contains an azide tag at the sn-1 position of the lipid headgroup. Direct functionalization of this compound with a range of reporter groups has been performed to illustrate the facile access to probes of use for characterizing binding. Quantitative lipid-binding studies using protein kinase C, a known DAG-binding receptor, demonstrate that these probes are active mimetics of natural DAG. Thus, these DAG probes will serve as robust sensors for studies aimed at understanding binding interactions and as precursors for the development of analogous probes of more complex phospholipids and glycolipids. |
| Databáze: | OpenAIRE |
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