The coming talk on July 30, 2008 (Wednesday)

Dr. Miao Wang will give us a talk on the importance of translational medicine in modern drug discovery.

Prostanoids are a class of small lipid molecules with diverse physiological and pathological function. They are synthesized from cell membrane-released arachidonic acid under sequential enzymatic actions. Cyclooxigenases (COXs) are rate-limiting enzyme in the biosynthesis and are targeted by non-steroidal anti-inflammatory drugs (NSAIDs), like aspirin and ibuprofen. Efficacy and toxicity consideration has been driving drug discovery of new NSAIDs. As such, COX-2 selective inhibitors were developed, however, recent clinical trials show increased cardiovascular toxicity is associated with these drugs. The function of prostanoids in cardiovascular system will be discussed, with particular focus on a new drug target in the COX pathway.

Hope to see you at CRB 302, 12:00 - 1:30 PM on Wednesday (July 30, 2008)! Snacks and water are provided. Lunch boxes are welcome.

The coming talk on July 16, 2008 (Wednesday)

Ms. Yao Zhang, a PhD candidate in the Department of Chemistry at UPenn, will talk about transmembrane proteins on next Wednesday (July 16, 2008).

 

Title: Molecular design of TM helical bundle as a tool for probing the feature that drives folding in membrane

The interaction of transmembrane helices is a fundamental step in the folding of membrane proteins. However, the energetics of interaction of transmembrane segments is not completely understood. We are interested in investigating the effect of the amino acid composition at the association interface, using a model peptide (MS1) derived from the soluble coiled coil GCN4-P1. Previous research in water soluble coiled coils showed that the stability of association increases with the hydrophobicity of the amino acid in the /a/ position. Here we have introduced Gly, Ala, Val and Ile at all the putative /a/ positions in MS1 and measured the dimerization equilibria of all variants using a disulfide crosslinking equilibrium method. The results show that the association strength ranks in a reversed order as in the water soluble peptides, consistent with both the fact that hydrophobic interactions are not dominant in the membrane environment and that small residues can be favorable at protein-protein interfaces in membrane proteins. Computational modeling of the MS1 variants suggest smaller amino acids allow for closer and more favorable backbone interactions than the larger amino acids.

Sounds a little bit Greek to you? Come and ask questions!

Hope to see you at CRB 302, 12:00 - 1:30 PM on Wednesday (July 16, 2008)! Snacks and water are provided. Lunch boxes are welcome.

(Figure is from http://www.scientificblogging.com/)