Department of Chemistry

The pursuit of transformational medicines

The DiMarchi laboratory has made contributions to advance discovery and development of specific drugs, such as Humulin®, Humatrope®, rGlucagon®, Humalog®, Evista® and Forteo®. The primary focus of current research is the integration of macromolecules and conventional small molecules to achieve transformational pharmacology. Glucagon, Glucagon-like Peptide-1 (GLP-1), and Glucose-dependent Insulinotropic Polypeptide (GIP) are regulatory hormones responsible for maintaining control of metabolism, most notably glucose homeostasis. A series of novel peptides which exhibit high potency and balanced activity across these three receptors have demonstrated superior, sustained efficacy in lowering body weight and glucose in animal models. These pre-clinical results established the basis for several ongoing human studies with specific mixed agonists. Additionally, a set of peptide-estrogen conjugates possessing full GLP-1 agonism with linker chemistries that enable differential estrogen release consistently proved to be more efficacious and safer in lowering body weight than the comparable controls.

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International award for HIV-1 research

A team led by Bogdan Dragnea has been awarded a three-year research grant by the international Human Frontier Science Program for study of processes involved in the self-assembly of HIV-1. Dragnea’s approach is to understand and interfere with the stages of the virus life cycle by gaining knowledge of the structural properties of virus assembly intermediates. Dragnea's project, "Physical principles in the self-assembly of immature HIV-1 particles," will examine assemblies, such as the one shown in the figure of HIV 1 Gag proteins assembling on the surface of a gold sphere. The research team includes groups led by Alan Rein of the National Cancer Institute in Frederick, Md., Paul Van der Schoot of the University of Twente in Netherlands and Dmitri I. Svergun of the European Molecular Biology Laboratory in Hamburg, Germany.

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Direct fluorescent labeling of live bacterial cells

Bacterial resistance is a rapidly emerging public health threat that underscores the need for development of novel antibiotic agents with new modes of action. The bacterial cell wall has been an attractive target for the development of antibiotics, but there are limited methods that allow direct visualization of active sites of cell growth and no methods to assess antimicrobial activity in situ. Recently, Professor Michael VanNieuwenhze and Professor Yves Brun (Biology) have developed a one-step method to label zones of growth in live bacterial cells. The method relies upon the ability of the bacterial cell to incorporate fluorescently-modified D-amino acids into its cell wall. This method has been applied to a broad array of evolutionarily diverse bacteria and it provides a powerful new tool for development of a better understanding of the basic mechanisms of bacterial growth and how it may be modified in response to environmental factors.

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