Robert Reynolds. Research Professor
Chemistry Building 221
(205) 934-9547

Research and Teaching Interests: Organic and Medicinal Chemistry, Rational Drug Design, Infectious Diseases and Cancer

Office Hours: By appointment

  • BS, University of Virginia, General Chemistry
  • PhD, Duke University, Organic Chemistry

I received a BS in Chemistry from the University of Virginia in 1977 and a PhD from Duke University in 1985.  While a student at Duke University under Dr. Barbara Shaw in Chemistry and Dr. David Sedwick in the Department of Medicine, I obtained a diverse education in experimental design and basic research covering topics from cell culture, protein isolation and gel electrophoresis to organic synthesis and drug design.

After a brief postdoctoral fellowship at NIEHS in the Research Triangle Park with Dr. Robert London in the area of deuterated probe development for in vivo NMR metabolism, I began a 25-year career in drug design and synthesis at Southern Research Institute in Birmingham, Alabama, advancing to the position of Director of Drug Discovery Technology. Although involved in numerous diverse programs from chemical education and outreach, optimization of Bath and Body Works bubble baths, chemical and biological diversity acquisition, and high throughput drug discovery technology, my major areas of emphasis were medicninal chemistry and new target and drug discovery against cancer and infectious diseases, particularly tuberculosis.

In 2012, I joined the University of Alabama at Birmingham to pursue a long time dream of supporting advanced education while also focusing on independent research in drug design against cancer and infectious diseases.

Curriculum Vitae

I have broad research interests from pure organic synthesis and the generation of novel, biologically relevant chemical diversity to medicinal chemistry and drug design targeting cancer and underserved diseases such as tuberculosis. 

Currently, my programs primarily involve drug design against single and essential targets in Mycobacterium tuberculosis including the asparyl-t-RNA synthetase (AspS), filamenting temperature sensitive protein Z (FtsZ), D-alanyl-D-alanine ligase (Ddl) and the highly related cell wall ligases MurC-F (crucial enzymes in cell wall biosynthesis), and shikimate kinase (MtSK). 

Many of these proteins are ATP dependent, highlighting my recent focus on analyzing and understanding the complete mycobacterial ATP binding proteome (ATPome) as an ideal and essential set of proteins for new drug development against tuberculosis. These proteins are essential for a variety of crucial cellular processes from environmental sensing and metabolic adaptation (the Pkn serine-threonine protein kinases) to energetic and catalytic pathways (topoisomerases, gyrases and cell wall attendant ligases such as Ddl and MurC-F). Furthermore, this area is timely with the rich datasets and protein structures available relating to the human kinome, allowing comparative inhibitor and crystal structure analyses in order to develop selective agents that target the bacterial proteins only.

Finally, and relating to my early interests and roots in anticancer drug discovery, I have begun a collaboration with Dr. Zaneta Nikolovska-Coleska, the University of Michigan, investigating the epigenetic target Disruptor-of-Telomeric-Silencing-1-Like (DOT1L) protein. This early stage program has identified novel drug–like non-nucleosides that may represent significant potential for development of new drugs targeting this crucial histone methyltransferase in mixed lineage leukemias (MLL). Optimized small molecules may have advantages over the current, first-in-class clinical agent Pinometostat that demonstrates typical issues of nucleoside-based drugs (poor bioavailability and significant hepatic metabolism and clearance).
  • Koneczny, I.; Schulenburg, A.; Hudec, X.; Knöfler, M.; Holzmann, K.; Piazza, G.; Reynolds, R.; Valent, P.; and Marian, B. Autocrine Fibroblast Growth Factor 18 Signaling Mediates Wnt-Dependent Stimulation of CD44-Positive Human Colorectal Adenoma Cells. Mol Carcinog. 2014, doi:10.1002/mc.22146.
  • Moukha-Chafiq, O.; Reynolds, R. C. Synthesis of novel peptidyl adenosine antibiotic analogs. Nucleosides Nucleotides and Nucleic Acids, 2014,33(2), 53-63.
  • Moukha-Chafiq, O.; Reynolds, R. C.  Parallel Solution Phase Synthesis and General Biological Activity of a Uridine Antibiotic Analog Library. ACS Comb. Sci., 2014 May 12, 16(5), :232-7.
  • Ekins, S.E.; Pottorf, R.; Reynolds, R. C.; Williams, A.J.; Clark, A.M.; Freundlich, J.S.  Looking Back To The Future: Predicting In vivo Efficacy of Small Molecules Versus Mycobacterium tuberculosis. J. Chem. Inf. Model., 2014 Apr 28, 54(4), 1070-82.
  • Pathak, A.K.; Pathak, V.; Reynolds, R. C.  Solution Phase Parallel Synthesis of Acyclic Nucleoside Libraries of Purine, Pyrimidine and Triazole Acetamides.  ACS Comb. Sci. 2014, 16, 485−493.
  • Ekins, S.; Freundlich, J.S.; Reynolds, R. C.  Are Bigger Datasets Better for Machine Learning? Fusing Single-Point and Dual-event Dose Response Data For Mycobacterium tuberculosisJ. Chem. Inf. Model. 2014, Jul 28, 54(7), 2157-65.
  • Moukha-Chafiq, O. and Reynolds, R. C.   Synthesis and general biological activity of a small adenosine-5'-(carboxamide and sulfanilamide) library.  Nucleosides Nucleotides and Nucleic Acids, 2014 Nov 2, 33(11), 709-29.
  • Gurcha, S.S.; Usha, V.; Cox, J.A.; Futterer, K.; Abrahams, K.A.; Bhatt, A.; Alderwick, L.J.; Reynolds, R. C.; Loman, N.J.; Nataraj, V.S.; Alemparte, C.; Barros, D.; Lloyd, A.J.; Ballell, L.; Hobrath, J.V.; Besra, G.S.  Biochemical and Structural Characterization of Mycobacterial Aspartyl-tRNA Synthetase AspS, a Promising TB Drug Target. PLoS One, 2014 Nov 19, 9(11), e113568.
  • Clark, A. M.; Dole, K.; Coulon-Spektor, A.;  McNutt, A.; Grass, G.; Freundlich, J. S.; Reynolds, R. C.;  Ekins, S.  Open Source Bayesian Models. 1. Application to ADME/Tox and Drug Discovery Datasets.  J. Chem. Inf. Model. 2015, 55, 1231−1245.
Full List of Publications