Skip to main content
Skip to main menu Skip to spotlight region Skip to secondary region Skip to UGA region Skip to Tertiary region Skip to Quaternary region Skip to unit footer

Slideshow

Confronting Pathogens with a Combination of Synthetic and Analytical Chemistry

Photo of guest speaker Prof. Roman Manetsch
Prof. Roman Manetsch
Associate Professor, Chemistry and Chemical Biology
Northeastern University
iSTEM Building 2, Room 1218
Organic Seminar

The Manetsch laboratory focuses on synthetic chemistry and the development of LC/MS-guided medicinal chemistry approaches for the development of anti-infective agents. The first half of the seminar focuses on the streptothricin natural products class, while kinetic Target-Guided Synthesis (kTGS) is the topic of the second half of the seminar.

Diagram illustrating common structures present in streptothricins

Streptothricins are highly active against gram-positive and gram-negative ESKAPE pathogens. Common within each streptothricin are a carbamoylated gulosamine sugar core, a streptolidine lactam moiety, and a β-lysine homopolymer of varying unit length. We have completed a convergent, diversity-enabling total synthesis of streptothricin consisting of 35 total steps and an overall yield of 0.40%. Our convergent strategy relies on two key disconnections at the C7 and C8 amines on the gulosamine core. Deriving from these disconnections, we assembled three fragments resembling each of the three key moieties of streptothricin F. These fragments are joined together in a set of late-stage coupling reactions to form the streptothricin F backbone. Using this fully developed streptothricin F synthesis, we are pursuing the synthesis of both previously reported and novel analogs of the streptothricin class.

Diagram illustrating Kinetic TGS process

Kinetic TGS was conceptually described in the early 1980s, nevertheless it is still relatively unexplored. In kinetic TGS, the biological target is actively engaged in the irreversible assembly of its own inhibitory bidentate ligand from a pool of smaller reactive fragments. The screening method can be as simple as determining whether or not the inhibitory product has been formed in a given test mixture. The design, development and optimization of the first kinetic TGS approach for the identification of compounds disrupting protein-protein interactions is discussed. In proof-of-concept studies, we demonstrated that the sulfo-click reaction, a bio-orthogonal amidation reaction between thio acids and sulfonyl azides, is suitable for large-scale, kinetic TGS targeting the protein-protein interactions of the Bcl-2 family. We are currently screening enzymatic and protein-protein interaction targets for the identification of anti-infectives using our optimized kinetic TGS method.

Research Areas:

Support Us

We appreciate your financial support. Your gift is important to us and helps support critical opportunities for students and faculty alike, including lectures, travel support, and any number of educational events that augment the classroom experience. Click here to learn more about giving.

Every dollar given has a direct impact upon our students and faculty.

Got More Questions?

Undergraduate inquiries: chemreg@uga.edu 

Registration and credit transferschemreg@uga.edu

AP Credit, Section Changes, Overrides, Prerequisiteschemreg@uga.edu

Graduate inquiries: chemgrad@uga.edu

Contact Us!

Assistant to the Department Head: Donna Spotts, 706-542-1919 

Main office phone: 706-542-1919 

Main Email: chem-web@franklin.uga.edu

Head of Chemistry: Prof. Jason Locklin