Peterson Research Group | Bio-Organic Chemistry

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Spring 2013: Chris Grubb ′14, Gabrielle Bailey ′15, Sarah Malkowski ′14, Noah Brown ′14.

One of our current projects involves studying the selectivity of cytosolic sulfotransferases (SULTs). These enzymes catalyze the transfer of a sulfuryl moiety (-SO3) from an activated sulfate group, 3’-phosphoadenosine-5’-phosphosulfate (PAPS), to a sulfate acceptor, usually an aliphatic or aryl alcohol. SULTs play a critical role in the regulation of the levels and activities of human neurotransmitters and hormones, as well as the excretion and detoxification of xenobiotics, including drugs and food additives.  As an example of the enzyme’s utility, >90% of dopamine in the human body circulates as dopamine sulfate. Although members in each SULT subfamily share considerable sequence and structural similarity, they appear to have dissimilar biological functions; there is little known about the factors that govern the substrate selectivity of these enzymes. We are currently synthesizing dopamine analogues and will subsequently analyze the enzyme’s ability to sulfate these analogues in an enzymatic assay in order to elucidate the molecular basis of the observed selectivity. We are excited to be collaborating with Prof. Cafiero’s group and are looking forward to correlating the enzymatic assay data with their computational data.

Another current project in our lab involves the design and synthesis of inhibitors of the enzyme LpxC. Generally, Gram-negative bacteria are more resistant to antibacterial therapeutics due to the intrinsic impermeability of their outer membrane. Additionally, lipid A, a key component of the lipopolysaccharide (LPS) in the outer membrane, is a potent toxin that results in septic shock and high mortality when it is released from dying bacteria. In 2010, septicemia (release of LPS) was the number ten cause of death in the country. In the biosynthetic pathway of Lipid A, the enzyme LpxC is responsible for catalyzing the first committed step of the mechanism. The LpxC active site has three key features: a hydrophobic passage, a zinc ion, and a polar region. Using this information and the structure of the natural substrate, we plan to further investigate the active site through docking studies and the synthesis of natural substrate analogues.

 

We are also currently collaborating on a project with Dr. Sébastien Ulrich at Institut des Biomolécules Max Mousseron (IBMM) at Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM) in Montpellier, France. Jennifer Rote, a current Rhodes junior,  spent 8 weeks in the summer  of 2013 in his laboratory working on a related project.

 


 

Group Members

Gabrielle Bailey, Chemistry 2015

Year: Junior
Major:  Chemistry
Minor:  Religious Studies
Hometown:  Springfield, MO
Favorite Piece of Glassware:  5 mL beaker
Other activities: St. Jude volunteering, Catholic Student Association, tennis, American Chemical Society, Gamma Sigma Epsilon Chemistry Honors Society
Project: Investigating the Selectivity of Human Cytosolic Sulfotransferase SULT1A3
Plans after Rhodes: Medical School

Conference Presentations:  

245th American Chemical Society National Meeting, April 7-11, 2013:
N.S. Brown, G.E. Bailey, L.W. Peterson. Synthesis of Dopamine Analogues to Investigate the Selectivity of Human Cytosolic Sulfotransferase SULT1A3. Poster-42 2013 Undergraduate Research & Creative Activity Symposium, Rhodes College, April 26, 2013.

Noah Brown, BMB 2014 

Year: Senior
Major: Biochemistry and Molecular Biology
Hometown: Charlotte, NC
Favorite Piece of Glassware: Sep Funnel
Other activities: Cross Country and Track
Project: Investigating the Selectivity of Human Cytosolic Sulfotransferase SULT1A3
Plans after Rhodes: Medical School

Conference Presentations:

245th American Chemical Society National Meeting, April 7-11, 2013:

Christopher Grubb, Chemistry 2014

Year: Senior
Major: Chemistry and Music
Hometown: Fort Worth, TX
Favorite Piece of Glassware: Buchner Funnel
Other activities: Resident Assistant, Rhodes Singers, Relay for Life
Project: Synthesis of Natural Substrate Analogues of the Enzyme LpxC
Plans after Rhodes: Medical School

Conference Presentations:

S. N. Malkowski, C. S. Grubb, L. W. Peterson. “Synthesis of Natural Substrate Analogues to Probe the Active Site of LpxC in Gram-negative Bacteria” ORGN-257 245th National American Chemical Society Meeting, New Orleans, LA, April 7-11,2013.

C.S. Grubb, S.N. Malkowski, L.W. Peterson. “Investigating the Active Site of LpxC in Gram-Negative Bacteria: Synthesis of Natural Substrate Analogues” Oral 33rd Annual Undergraduate Research Conference. Memphis, TN, February 23, 2013.

C.S. Grubb, S.N. Malkowski, L.W. Peterson. “Synthesis of Natural Substrate Analogues to Probe the Active Site of LpxC in Gram-negative Bacteria" Poster-36 2013 Undergraduate Research & Creative Activity Symposium, Rhodes College, April 26, 2013

 

Sarah Malkowski, Chemistry 2014

Year: Senior
Major: Chemistry
Hometown: Oviedo, FL
Favorite Piece of Glassware: Everything in baby form
Other activities: Tutoring, SOS Mentor, ACS Student Club
Project: Synthesis of Natural Substrate Analogues of the Enzyme LpxC; Investigating the Selectivity of Human Cytosolic Sulfotransferase SULT1A3
Plans after Rhodes: MD/PhD

Conference Presentations:

S. N. Malkowski, C. S. Grubb, L. W. Peterson. “Synthesis of Natural Substrate Analogues to Probe the Active Site of LpxC in Gram-negative Bacteria” ORGN-257 245th National American Chemical Society Meeting, New Orleans, LA, April 7-11,2013.

C.S. Grubb, S.N. Malkowski, L.W. Peterson. “Investigating the Active Site of LpxC in Gram-Negative Bacteria: Synthesis of Natural Substrate Analogues” Oral 33rd Annual Undergraduate Research Conference. Memphis, TN, February 23, 2013.

C.S. Grubb, S.N. Malkowski, L.W. Peterson. “Synthesis of Natural Substrate Analogues to Probe the Active Site of LpxC in Gram-negative Bacteria" Poster-36 2013 Undergraduate Research & Creative Activity Symposium, Rhodes College, April 26, 2013