Stereoselective Total Synthesis of (-)-Renieramycin T.

A stereoselective total synthesis of (-)-Renieramycin T (1t) from a key tetrahydroisoquinoline intermediate previously utilized in our formal total synthesis of Ecteinascidin 743 is described. The synthesis features a concise approach for construction of the pentacyclic framework using a Pictet-Spengler cyclization of bromo-substituted carbinolamine 17, which obviates the regioselectivity problem of the Pictet-Spengler cyclization. The results of cytotoxicity studies are also presented.

Development of agents that modulate protein-protein interactions in membranes.

Membrane proteins account for approximately one third of all proteins in eukaryotic and prokaryotic cells. These proteins are critical in a diverse array of cellular functions. Despite their obvious importance, the effectiveness of research tools to study the structure and function of integral membrane proteins lags behind that of water-soluble proteins. This is due in part to the lack of probing agents that can specifically and selectively recognize these targets. This review focuses on methods developed to overcome the obstacles of studying membrane proteins. We describe TM protein properties as well as biophysical properties of amino acids within the membrane bilayer. We also summarize the known characteristics of membrane regions in their distinctive environments and generate a summary of current research approaches that succeed in probing interactions of TM proteins within their native setting. This allows further insight into protein-protein interactions in a hydrophobic environment as it pertains to drug development.