Cottrell College Science Awards - 2015
Characterizing the Molecular Interactions between Carrier Proteins and Oxygenases in Natural Product Biosynthesis
Advanced chemical research often involves trying to understand the precise interactions – and there are seemingly an infinite number of these interactions -- that occur among the smallest particles of matter, atoms and molecules.
For example, Louise Charkoudian, an assistant professor of chemistry at Haverford College, has received a Cottrell College Science Award from Research Corporation for Science Advancement to help her understand the mechanisms by which certain bacteria – tiny one-celled organisms – may be able to help create “biaryl bonds.”
In other words, she is looking at how these living cells use chemistry to create double (– “bi” –) atomic bonds among an important class of molecules that incorporate aromatic rings (“aryls” in chemspeak).
Fundamentally, these ringed molecules are essentially various kinds of hydrocarbons, that is, molecules composed of hydrogen and carbon atoms. One well-known chemical in this class is benzene. (The term “aromatic” was used for the substances arising from these ring-shaped molecules because early chemists considered them to be sweet smelling, although the term is now used to refer to molecular stability.) But Charkoudian’s target molecules also contain non-carbon and non-hydrogen atoms as well and therefore are not technically considered to be hydrocarbons.
“The biaryl structure is a predominant feature in many pharmaceutically relevant and biologically active compounds,” Charkoudian notes. “As a result, for over a century organic chemists have sought to develop new and more efficient biaryl bond-forming methods.”
By understanding precisely how bacteria may be able to create double bonds among these ringed-molecules, Charkoudian and her students may be opening pathways for other researchers to create new molecules for medicine.
Specifically, they hope to peer deep inside the intricate processes of bacteria to observe how a specific oxygenase, a protein capable of changing the oxidation states of molecules, recognizes and reacts to a specific peptide, a short chain of amino acid molecules, to form the biaryl bonds.
To do so they will call on techniques from the fields of organic chemistry, molecular biology, biochemistry and biophysical chemistry.