"Applying conventional disciplines of chemistry to current and future issues."

Drug Design & Delivery

microscopic view of a compound

Professor Acey's group is studying competitive inhibitors of acetyl- and butyrylcholinesterase. A number of these compounds are currently used in the treatment of Alzheimer's disease (AD). Cholinesterases are responsible for the enhanced hydrolysis of acetylcholine and loss of cognitive function in Alzheimer's patients. In addition, the cholinesterases have been implicated in amyloid plaque formation. In collaboration with the Nakayama and Sorin Labs, Dr. Acey's group is developing a class of irreversible cholinesterase inhibitors that could be used to raise the level of acetylcholine in AD patents and/or prevent the formation of neural plaques. Recently, a number of autistic children have been reported to respond favorably to compounds used to treat AD patients. As such, we are hoping our compounds might eventually be used for the treatment of autism.

ball and stick model of a compound

Lijuan Li's research program focuses on the chemistry of nitric oxide and of its transition metal complexes of biological interests. They reported a family of nitrosyl non-heme-iron compounds with g values of 2.03 and also prepared several iron-sulfur nitrosyl clusters. These compounds are known to be closely associated with the activity of nitric oxide (NO) in human physiology, some of which include controlling blood pressure, preventing platelet aggregation, killing invading microorganisms, and a number of other essential bodily functions. The objectives are to investigate the possibility for these complexes acting as NO-donor drugs and to examine their potentials to be delivered to a targeted DNA.

cartoon display of a biological molecule

Kensaku Nakayama's group is involved in the design and synthesis of a series of organophosphorus-based inhibitors that are highly selective for butyrylcholinesterase (BuChE) and which do not affect acetylcholinesterase activity. Butyrylcholinesterase is known to be over-expressed in patients with Alzheimer's disease (AD) and so it is the primary enzyme responsible for acetylcholine hydrolysis in the CNS of these patients. Therefore, these compounds may show promise as effective therapeutic agents or drugs to prevent or treat cognitive loss in AD patients. Dr. Nakayama's group is currently developing a library of second-generation inhibitors with enhanced selectivity and inhibitory properties by incorporating the results from virtual screening studies though molecular simulations. This work is currently being conducted collaboratively with biochemist, Dr. Roger Acey (CSULB) and physical chemists, Drs. Katherine Kantardjieff (Cal Poly Pomona) and Eric Sorin (CSULB).

representative structure of a drug

Michael Schramm's research group employs molecular recognition in drug design. Molecular recognition is the study of how and why molecules interact. At its essence lies the attraction of molecules at energy levels weaker than covalent. Hydrogen bonding, metal coordination, and the hydrophobic effect cover some of these possible forces. In nature there are countless crucial interactions predicated on noncovalent interactions such as enzyme-substrate recognition, DNA-protein binding, and ion-receptor transport. From a synthetic point of view these principles have strongly influenced areas of research from drug design to materials science to molecular self-assembly. Michael Schramm's research uses molecular recognition as a design principle to develop new synthetic molecules that are compatible with and capable of regulating biological function.

structure of a collagen inspired material

Kasha Slowinska's group is focused on understanding the structure/property relationship of collagen-inspired materials intended as potential drug delivery matrixes. They investigate the relationship between the structure of collagen composites and their mechanical/dynamic behavior and transport properties. Moreover the helical peptides are used to better control the drug delivery rate. They are also interested in development of new experimental methods to study transport in complex media. Techniques used in the lab include synthetic methods, SEM, TEM, FRAP, DSC, CD, Electrochemistry, Microfabrication, Cell culture, and Bioassays.

structure of a nanoparticle based material

Young Shon's group targets the preparation of a new novel multifunctional nanoparticle system that can provide a better stability and biocompatibility. The target nanocarrier is the gold nanoparticle-cored dendrimers (NCDs) linked with fluorophore in the interior and cancer specific targeting groups in the exterior. The NCDs are composed of nontoxic materials and will resist aggregation in biological fluids due to the presence of biocompatible dendron shells. Cancer specific targeting groups will guide the gold NCDs specifically to the tumor sites. In addition, gold core can be locally heated by a non-invasive induction heater and act as local heat sources that can destroy tumor tissues. These unique structural properties of NCDs make them ideal candidates for use as a multifunctional platform that allows targeting, imaging, and killing of cancer cells.

generative structure of a protein conformation
logo of Dr. Sorin's website

Eric Sorin's group applies computational tools to examine the structure, stability, and dynamics of biological molecules of varying sizes and chemical compositions. Specific topics being studied in this lab include protein and RNA folding and misfolding, the development of accurate all-atom models for lipid membrane simulation, and enzyme-inhibitor interactions relevant to drug design. They apply a variety of models and methods, with a focus on Molecular Dynamics, and utilize the Folding@Home Distributed Computing resource to sample large numbers (tens of thousands) of independent simulations. These tools have allowed them to examine fundamental protein and RNA folding processes in detail, and to assess the effects of bulk ensemble averaging on the kinetics and mechanisms of interest, thus bridging the gap between single-molecule and bulk experimental measurements. This massive computational power allows them to examine differences that may arise based on changes in the molecular system being studied, the model being employed, and the environmental conditions being modeled.