The Borhan group focuses on several different research areas, including organic methodology, natural product synthesis, bioorganic mechanisms, and computational studies.
Our research interests cover the interface of chemistry and biology. The central theme of our work is geared towards the elucidation of enzymatic mechanisms and the interaction of bioactive compounds with biopolymeric receptors and enzyme systems. In pursuit of our goals we depend heavily on the synthesis of bioactive analogs to study the behavior of different biological processes. We are also keen on developing new techniques for isolation and identification of receptors which are usually very low in concentration in vivo.
Protein-substrate interaction projects
A main focus of our research is whether or not the position of putative negative charge can regulate wavelength absorption of retinoids. In particular, we are interested in the enzymatic mechanism of ß-carotene 15,15’-dioxygenase, responsible for the conversion of ß-carotene to retinal, and retinol isomerohydrolase
which catalyzes the isomerization of all-trans-retinol to 11-cis-retinol. Our efforts in the area of protein/substrate interaction
are focused on the case of wavelength regulation by Rhodopsin. Different types of rhodopsin in mammalian eyes contain 11-cis-reti-
nal as the light sensitive chromophore with absorption maxima ranging from ~400 nm to ~600 nm. We are interested in understanding how different rhodopsin pigments regulate wavelength absorption with the same chromophore. We hope to gain insight into this system by engineering rhodopsin protein mimics capable of binding retinal and rationally propose mutagenesis of amino acid residues within the binding pocket of the surrogate protein in hopes of reproducing the
interaction of different visual rhodopsins and 11-cis-retinal.
Chiral recognition host-guest chemistry
An extension of understanding the interaction of biological receptors with small molecules has led us to investigate the design of artificial receptors and host-guest systems in which chiral recognition by the host can lead to absolute stereochemical determination of chiral centers. In our system the chromophoric receptors are reporters of chirality. Their binding to small chiral guest molecules forms a chiral complex that is observable by exciton-coupled circular dichroism (ECCD) spectroscopy.
Formation of THF diols
We are also engaged in the study of a new class of fatty acid metabolites, THF-Diols of Arachidonic Acid, which can trigger the release of Ca2+ within cells. We are pursuing the enantiospecific synthesis of these compounds and developing new techniques for isolation and identification of the receptor responsible for initiating the biological activity of AA-THF-diols.