| Hubert Yin’s research interests lie
at the interface of chemistry and biology with particular
focus on structure-based drug design and membrane protein
regulation.
1. Drug Discovery: Pain remains a significant public health
issue with two-thirds of patients achieving little to no pain
relief from the myriad of currently available pharmacotherapies
and dosing regimens. The use of opioid (e.g. morphine) pharmacotherapies
produces several rewarding and reinforcing side effects, which
result in the drugs’ diversion to abuse settings. Glia
cells were found to play a critical role in initiating and
maintaining increased nociception in response to peripheral
nerve injury. The opioids-induced glial cell activation attenuates
opioid-induced pain suppression and enhances the development
of opioid tolerance and dependence, the drug reward, and other
negative side effects such as respiratory depression. We are
interested in employing rational design as well as in vitro
and in vivo high-throughput screening techniques to identify
novel small-molecule inhibitors of the cell surface receptors
that regulate glical cell activation. The identified agents
will potentially serve as therapeutics that suppresses opioid-dependence
and tolerance.
2. Biotechnology Development: Membrane proteins transmembrane
domains play pivotal roles in many biological processes. However,
the protein-protein interactions in the membrane is little
understood due to the lack of exogenous agents that can recognize
these transmembrane regions with high specificity and selectivity.
Conventional tools such as antibodies are unable to bind to
the transmembrane regions of membrane proteins. A second project
in our lab is to develop exogenous peptide and small-molecule
agents that target transmembrane helices. Using these agents,
we can study these important membrane protein-protein interactions,
thereby further our understanding of molecular recognition
in membranes.
Selected Publications:
Caputo, G. A.; Litvinov, R. I.; Li, W.; Bennett, J. S.; DeGrado,
W. F.; Yin, H. “Computationally Designed Peptide Inhibitors
of Protein-Protein Interactions in Membranes”, Biochemistry
2008, 47, 8600-8606.
Slivka, P. F.; Wong, J.; Caputo, G. A.; Yin, H. “Peptide
Probes for Protein Transmembrane Domains”, ACS Chem.
Biol. 2008, 3, 402-411.
Yin, H. “Exogenous Agents that Target Transmembrane
Domains of Proteins”, Angew. Chem. Int. Edit. 2008,
47, 2744-2752.
Yin, H.; Slusky, J. S; Berger, B. W.; Walters, R. S.; Vilaire,
G.; Litvinov, R. I.; Lear, J. D.; Caputo, G. A.; Bennett,
J. S.; DeGrado, W. F. “Computational Design of Peptides
that Target Transmembrane Helices”, Science 2007, 315,
1817-1822.
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