Amino acids are the building blocks of proteins and are used in peptide drugs. Naturally occurring amino acids have relatively simple side chains (defining structure). Synthetic amino acids can have complex side chains.

Vlad Kumirov, an undergraduate at the University of Arizona, used novel methods in organic chemistry to synthesize chiral gamma-unsaturated alpha-amino acids. He worked with graduate student Zhihua Liu in Dr. Victor J. Hruby's lab last summer. These amino acids can be inserted into peptides or proteins to better understand structure-activity relationships. The methodology used for the synthesis is part of a project in the Hruby lab that aims at discovering new ways to make small organic molecules, like amino acids. Hongchang Qu - a recent Ph.D. graduate, and Zhihua Liu - a graduate student, have worked on the project previously to develop these methods. Vlad Kumirov continued the project with Zhihua Liu after Dr. Qu graduated.

The synthesis starts with glycine, which is the only natural non-chiral amino acid. It is converted to a form that reacts with other molecules with specific structures. The end result is an amino acid with a side chain that preserves the conformation of the molecule that it was reacted with. The side chain itself is chiral (having a specific asymmetry) and has a double-bond on the end. These side chains change the structure of peptide drugs, and could change their function. Understanding the relationship between the two is one of the most important aspects of drug design. Having a simple way of making these unique amino acids would aid developing better peptide drugs.

Vlad's work on the synthesis of these amino acids was funded by Howard Hughes Medical Institute Grant to the Undergraduate Biology Research Program and by the U.S. Public Health Service Grant to Dr. Victor J. Hruby.

Vlad Kumirov, UBRPer in Dr. Victor Hruby's lab, Chemistry