Adegboyega (Yomi) K. Oyelere Assistant Professor Office: 3305 IBB Building Phone: 404-894-4047 Fax: 404-894-7452 E-mail Yomi Oyelere Research Group Website

B.Sc., University of Ibadan, Nigeria, 1992; Ph.D., Brown University, 1998; Jane Coffin Childs Postdoctoral Fellow, Yale University, 1998-2001; NIH Postdoctoral Associate, Yale University 2001

Nigerian Breweries Prize in Chemistry and Biochemistry for the Best Graduating Student, 1993; Lever Brothers (Nigeria) Prize for the Best Honors Degree Student in Chemistry, 1993; Faculty Prize for Best Final Year Student in the Faculty of Science, University of Ibadan, 1993; Elected to Sigma Xi, 1995; Richardson Fellowship for Outstanding Graduate Student, Brown University, 1997; Sigma Xi Award for Outstanding Graduate Student, Brown University, 1998; Jane Coffin Childs Postdoctoral Fellowship for Medical Research, Yale University, 1998; Blanchard Assistant Professorship, Georgia Institute of Technology, 2007.

Research Interests

Bioorganic Chemistry, Biochemistry and Drug Design. The overarching research objective of our laboratory is to delineate the chemical basis of the molecular recognition events employed by biomolecules to drive important biological processes and how perturbation of these events, by natural and synthetic ligands, can be used to understand the molecular basis of various human disease conditions, especially cancer, viral- and bacterial-infections; and to use the information gleaned from such perturbation studies to arrive at potentially new therapeutic solutions for these conditions. Individual research project involves a unique blend of the tools of synthetic organic chemistry with biochemistry and molecular biology. Enumerated below are specific interrelated research projects that are currently underway:

RNA-Small Molecule Interaction. RNAs adopt intricate and structurally diversed motifs susceptible to direct interactions by small molecules in similar manner to proteins. An atomic level understanding of RNA-small molecule interactions will aid identification of a myriad of biologically useful molecules including novel RNA structural probes; and new anti-viral, anti-tumor and antibacterial agents. One class of nucleic acid targeting drugs are the anthracyclines. Literature evidence suggests that anthracyclines partly derived their anti-tumor activities through DNA-intercalation mediated "poisoning' of the eukaryotes topoisomerase II. Despite their chemical similarity to DNA and direct role in gene expression, little is known about the extent to which RNA interactions with anthracyclines contribute to anthracyclines' biological activities. The primary objective of this research is to elucidate the molecular features essential for the interaction of anthracyclines with the iron responsive elements (IREs), the hairpin loops located in the untranslated regions of mRNAs encoding key proteins involved in iron metabolism; and the effects of such interactions on the formation of the crucial RNA-protein complexes that regulate intracellular iron homeostatis.

Targeted Histone Deacetylase (HDAC) Inhibition. One nucleic acid associated protein that is of current interest to us is the Histone Deacetylase (HDAC). HDACs and histone acetyltransferases (HATs) are two functionally opposing enzymes, which tightly regulate the chromatin structure and function via sustenance of equilibrium between the acetylated- and deacetylated-states of nucleosomal histones. Aberrations in intracellular histone acetylation-deacetylation equilibrium have been linked to the repression of a subset of genes resulting in excessive proliferation and are implicated in a number of malignant diseases. HDACs function as part of multiprotein complexes that catalyze the removal of acetyl groups from the -amino groups of specific lysine residues located near the N-termini of nucleosomal core histones. Inhibition of HDACs activity results in the weakening of the bond between histones and DNA, thus increasing DNA accessibility and gene transcription. This has recently been clinically validated as a new therapeutic strategy for cancer treatment with the FDA approval of SAHA for the treatment of cutaneous T cell lymphoma. To date, several other structurally distinct small molecule HDAC inhibitors have been reported, however, most of these agents non-selectively inhibit the deacetylase activity of class I/II HDAC enzymes. Toward improving the therapeutic index of current HDAC inhibitors, we are developing new HDAC inhibitors for targeted cancer therapy applications. Our goals here are two-fold: (1) to develop HDAC inhibitors that sensitize cancer cells to nucleic acid interacting anticancer drugs and (2) to develop methodology for cell type-selective delivery of HDAC inhibitors.

Design and Synthesis of Novel Bioconjugates for Molecular Delivery Applications. We are also investigating new molecular delivery systems for nanoparticles and small molecule drugs. In collaboration with Professor El-Sayed's group, we are developing new approaches for targeting gold nanorods into the nucleus of live cells. Additionally, we are exploring the periplasmic protein secretion pathway to deliver cell wall damaging agents to the bacterial periplasm. This effort could result in novel diagnostic and therapeutic strategies.

Recent Publications

Oyelere, A. K.; Chen, P. C.; Huang, X.; El-Sayed, I. H.; El-Sayed, M. A. Peptide-Conjugated Gold Nanorods for Nuclear Targeting. Bioconj. Chem. 2007, 18, 1490-1497.

Canzoneri, J. C.; Oyelere, A. K. Interaction of Anthracyclines with Iron Responsive Element mRNAs. Under Review.

Chen, P. C.; Emrich, R. E.; Patel, P. A.; Oyelere, A. K. Direct Diazo-Transfer Reaction on ?-lactam: Synthesis and Preliminary Biological Activities of 6-Triazolylpenicillanic Acids. Bioorg. Med. Chem. 2007, 15, 7288-7300.

Oyelere, A. K.; Chen, P. C.; Yao, L. P.; Boguslavsky, N. Heterogeneous Diazo-transfer Reaction: A Facile Unmasking of Azide Groups on Amine Functionalized Insoluble Supports for Solid Phase Synthesis. J. Org. Chem. 2006, 71, 9791-9796.

Cho, H.D.; Oyelere, A.K.; Strobel, S.A; Weiner, A. M., Use of nucleotide analogs by the CCA-adding enzyme (tRNA nucleotidyltransferase): deciphering the basis for nucleotide selection RNA 2003, 9, 970-981.

Strobel, S.A; Jones, F.D.; Oyelere, A.K.; Ryder, S.P., Biochemical detection of adenosine and cytidine ionisation within RNA by interference analysis. Nucleic Acids Res. Suppl. 2003, 3, 229-230.

Basu, S.; Oyelere, A.K., (2003),"The Role of Recombinant DNA Technology in Medicinal Chemistry and Drug Discovery", Burger's Medicinal Chemistry, Vol 2, Chapter 4, 82-113, D. Abraham (Ed.), John-Wiley.

Oyelere, A. K.; Kardon, J. R.; Strobel, S. A., pKa Perturbation in Genomic Hepatitis Delta Virus Ribozyme Catalysis Evidenced by Nucleotide Analogue Interference Mapping Biochemistry 2002, 41, 3667-3675.

Patent Applications

Oyelere, A.K., Farmer, J.J., Bifunctional Macrolide Heterocyclic compounds and methods of making and using same. EP. 2006/1682563 A1

Oyelere, A.K., Goldberg, J.A., Orbin, A., Salvino, J.M., Zhou, J. Biaryl heterocyclic amines, amides and sulfur-containing compounds and methods of making and using the same. EP. 2006/1664001 A2

Wang, D., Sutcliffe, J.A., Oyelere, A.K., McConnell, T.S, Ippolito, J.A., Abelson, J.N., Springer, D.M. et al, "Bifunctional Heterocyclic compounds and methods of making and using same." US 2005/0197334 A1

Wang, D., Sutcliffe, J.A., Oyelere, A.K., McConnell, T.S, Ippolito, J.A., Abelson, J.N., Springer, D.M. et al "Bifunctional heterocyclic compounds and methods of making and using same." EP. 2005/1543017 A2

Steitz, T.A., Moore, P.B., Sutcliffe, J.A., Oyelere, A.K., Ippolito, J.A. "Ribosome structure and protein synthesis inhibitors." U.S. 2005/0036997 A1.