|
We are currently interested in the areas of RNA processing, signal transduction and medicinal chemistry. However, no biological problem is safe from our chemical curiosity. Here is a list of recent projects of interest to the lab: During gene expression, the information stored in the DNA of the genome must first be transcribed into messenger RNA (mRNA) before it can be translated into a functioning protein. In eukaryotes, i.e. yeast and higher organisms, the mRNA is not merely a copy of the genomic DNA sequence. Rather, the primary transcript, or pre-mRNA, being a linear mosaic of coding and non-coding segments and much longer than the reading frame length of the gene being transcribed, must undergo extensive processing before being exported to the cytoplasm for translation. Pre-messenger RNA processing includes the capping, splicing, editing and cleavage/polyadenylation of the transcript. These processes are carried out by multi-molecular complexes, which include many proteins whose roles are not yet known. In particular, we are studying the role of protein phosphorylation in pre-mRNA 3' cleavage, which directly precedes poly(A) tail addition. In this project we use in vitro assays, molecular and cellular biology techniques and chemical biology to understand how 3' cleavage is regulated. Many G-protein coupled receptors (GPCRs), such as the OR-I7 olfactory receptor, specifically bind low-molecular weight compounds while carrying out their function as signal transduction membrane receptors. Because membrane proteins are difficult to crystallize, very little is known about the molecular recognition between the various GPCRs and their ligands. OR-I7 is also known as the octanal receptor because it binds this fragrant compound selectively. In this project we are using the OR-I7 receptor as a model GPCR to learn more about the molecular recognition details of olfaction. We are synthesizing a variety of octanal isosteres and conformationally restricted analogs to probe the range of weak intermolecular forces employed by OR-I7 and other GPCRs to recognize their ligands. The novel compounds we are making are tested for binding and agonism/antagonism of the OR-I7 receptor by our collaborators in the Stuart Firestein lab at Columbia University. [Project entails molecular modeling, organic synthesis and biochemical assay.] |
||
|
|||||||||
|
C8: Octanal, |
||