Anthony Bell

Assistant Professor

Biomedical Chemistry


Post-Doctoral; Harvard Medical School, Boston, MA (2005 – 2009)
Post-Doctoral; Columbia Medical School, New York, NY (2002 – 2004)
Ph.D.; New York University, New York, NY (1996 – 2002)
B.S.; Millsaps College, Jackson, MS (1990 – 1994)

Research interests:

  1. Screening side-chain modified and nonproteinogenic amino acids as new building blocks for ribosomal peptide synthesis.
  2. Elucidating protein – nucleic acid interactions that mediate peptide elongation.
  3. Developing short peptides at therapeutics to treat endothelial disorders such as Sickle Cell Disease and Atherosclerosis.
  4. Investigating novel protein – nucleic acid interactions to attenuate the role of DNA binding proteins in inflammation.

Current Research:

I am interested in using modified and nonproteinogenic (unnatural) amino acids to enhance the pharmacological properties of small peptides.  Peptides have long been sought after as drug molecules due to their high target binding specificity, high potency and low toxicity.  Despite these attributes, peptides have shown limited use as therapeutics due to their size and low oral bioavailability.  Low peptide bioavailability is largely the result of two phenomena:  (1) poor membrane permeability that reduces absorption into the gastrointestinal (GI) tract and (2) enzymatic degradation that occurs in the GI tract and the systemic blood circulation.  I believe that these pharmacological deficiencies can be overcome by using unnatural amino acids as substrates for peptide synthesis.

In nature microorganisms use large multi-subunit enzymes, nonribosomal peptide synthetases (NRPSs), to synthesize bioactive peptides with enormous chemical complexity.  These peptides, referred to as nonribosomal peptides (NRPs), contain numerous unnatural (i.e. D-amino, N-methyl and b-acids) and side-chain modified amino acids.  Unnatural amino acids provide enhanced protease stability and membrane permeability, while modified residues increase the chemical complexity of NRPs.  Given these properties, it is not surprising that there has been a great deal of effort to isolate/develop NRPs as drugs.  Notable NRPs are the antibiotics penicillin and vancomycin.

Despite recent advances in the cloning and expression of NRPSs, their size (100kDa to > 1MDa) and complexity make the reconstitution of these systems very difficult.  Hence, alternate methods are being investigated.  My approach is to use a reconstituted E. coli translation system (PURE system) to isolate therapeutic NRP-like peptides.  My experiments are designed to establish a set of biophysical criteria between amino acids and the E. coli translation machinery to serve as a threshold for translation.  I am currently developing novel kinetic and thermodynamic binding assays to detect the activation level(s) of amino acids (L- and unnatural) using aminoacyl-tRNA synthetases (AARSs).  These assays will set the initial criteria for translation.  I am also investigating the binding interactions between the bacterial translation factor EF-Tu and aminoacyl-tRNAs (L- and unnatural) to establish a binding affinity scale to predict translation.  These experiments will provide an increased level of stringency that will be used to establish a diverse set of unnatural and modified amino acids.  These amino acids will then be used in the PURE system to screen peptide libraries to isolate NRP-like peptide antagonists to treat endothelial disorders such as Sickle Cell Disease (SCD) and Atherosclerosis.