个人简介

2009 Carl Storm Underrepresented Minority Fellowship (GRC 2009, Bioorganic Chemistry). 2008 One of two Georgia Tech nominees for a Beckman Young Investigator Award 2007 Blanchard Assistant Professorship (Georgia Institute of Technology). 1998 Jane Coffin Childs Postdoctoral Fellowship for Medical Research. 1998 Sigma Xi Award for Outstanding Graduate Student with Potential for further Contribution to Science, Brown University. 1998 Admitted as a Graduate Member of The Royal Society of Chemistry. 1997 Richardson Fellowship for Outstanding Graduate Student, Brown University. 1995 Elected to Sigma Xi, The Scientific Research Society. 1993 Faculty Prize for the Best Final Year Student in the Faculty of Science, University of Ibadan (Nigeria). 1993 The Lever Brothers (Nigeria) Prize for the Best Honors Degree Student in Chemistry. 1993 The Nigerian Breweries Prize in Chemistry and Biochemistryfor the Best Graduating Student in Biochemistry and Chemistry

研究领域

Biochemistry/Chemical Biology/Medicinal Chemistry/Nanoscience and Technology/Organic Chemistry/Synthesis

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.

近期论文

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Gryder, B. E.; Akbashev, M. J.; Rood, M. K.; Raftery, E. D.; Meyers, W. M.; Dillard, P.; Khan, S.; Oyelere, A. K. Selectively Targeting Prostate Cancer with Antiandrogen Equipped Histone Deacetylase Inhibitors. ACS Chemical Biology, 2013 (Article ASAP). DOI: 10.1021/cb400542w. *Gryder, B.E.; *Rood, M.K.; *Johnson, K.A.; Patil, V.; Raftery, E.D.; Yao, L.D.; Rice, M.; Azizi, B.; Doyle, D.F.; Oyelere, A.K., Histone Deacetylase Inhibitors Equipped with Estrogen Receptor Modulation Activity. Journal of Medicinal Chemistry 2013, 56, 5782−5796 (*= these authors contributed equally to this work), DOI: 10.1021/jm400467w Guerrant, W.; Patil, V.; Canzoneri, J.; Hood, R.; Oyelere, A. K. Dual-acting histone deacetylase-topoisomerase I inhibitors Bioorg. Med. Chem. Lett. 2013, 23, 3283–3287. (article online) Patil, V.; Sodji, Q.; Kornacki, J.; Mrksich, M.; Oyelere, A. K. 3-Hydroxypyridin-2-thiones as a novel zinc binding group for selective HDAC inhibition. J Med Chem 2013, 56, 3492−3506. DOI: 10.1021/jm301769u jm-2012-01769u_0013 Gryder, B.; Sodji,Q. H.; Oyelere, A. K. Targeted Cancer Therapy: Giving Histone Deacetylase Inhibitors All They Need to Succeed. Future Med. Chem. 2012, 4, 505-524. DOI: 10.4155/fmc.12.3 *Dreaden, E.C.; *Gryder, B.E.; Austin, L.A.; Tene Defo, B.A.; Hayden, S.C.; Pi, M.; Quarles, L.D.; Oyelere, A.K.; El-Sayed, M.A., Antiandrogen Gold Nanoparticles Dual-Target and Overcome Treatment Resistance in Hormone-Insensitive Prostate Cancer Cells Bioconjugate Chemistry 2012, (*= these authors contributed equally to this work) DOI: 10.1021/bc300158k Patil, V.; Canzoneri, J. C.; Samatov, T. R.; Lührmann, R.; Oyelere, A. K. Molecular architecture of zinc chelating small molecules that inhibit spliceosome assembly at an early stage. RNA 2012, 18, 1605-1611. DOI: 10.1261/rna.034819.112 Dreaden, E. C.; Mwakwari, S. C.; Austin, L. A.; Kieffer, M. J.; Oyelere, A. K.; El-Sayed, M. A. Small Molecule-Gold Nanorod Conjugates Selectively Target and Induce Macrophage Cytotoxicity towards Breast Cancer Cells. Small 2012, 8, 2819-2822. DOI: 10.1002/smll.201200333 Guerrant, W.; Patil, V.; Canzoneri, J. C.; Oyelere, A. K. Dual Targeting of Histone Deacetylase and Topoisomerase II with Novel Bifunctional Inhibitors. J. Med. Chem. 2012, 55, 1465−1477. DOI: 10.1021/jm200799p Gryder, B.; Guerrant, W.; Chen, C. H.; Oyelere, A. K. Oxathiazole-2-one derivative of bortezomib: Synthesis, stability and proteasome inhibition activity. Med. Chem. Comm. 2011, 2, 1083–1086 DOI: 10.1039/C1MD00208B Huang, X.; Kan, B.; Qian, W.; Chen, P. C.; Oyelere, A. K.; El-Sayed, I. H.; El-Sayed, M. A. Comparative study of photothermolysis of cancer cells with nuclear-targeted or cytoplasm-targeted gold nanospheres: continuous wave or pulsed lasers. J. Biomed. Optics 2010, 15, 058002 DIO: 10.1117/1.3486538 Mwakwari, S. C.; Guerrant, W.; Patil, V.; Khan, S. I.; Tekwani, B. L.; Gurard-Levin, Z. A.; Mrksich, M.; Oyelere, A. K. Nonpeptide Macrocyclic Histone Deacetylase (HDAC) Inhibitors Derived from Tricyclic Ketolide. J. Med. Chem. 2010, 53, 6100–6111 DIO: 10.1021/jm100507q Mwakwari, S. C.; Patil, V.; Guerrant, W.; Oyelere, A. K. Macrocyclic Histone Deacetylase (HDAC) Inhibitors. Curr. Top. Med. Chem. 2010, 10, 1423-1440 DOI: 10.2174/156802610792232079 Oyelere, A. K. Macrocycles in Medicinal Chemistry and Drug Discovery (Editorial). Curr. Top. Med. Chem. 2010, 10, 1359-1360 Guerrant, W.; Mwakwari, S. C.; Chen, P. C.; Khan, S. I.; Tekwani, B. L.; Oyelere, A. K. A Structure Activity Relationship Study of the Antimalarial and Antileishmanial Activities of Non-peptide Macrocyclic Histone Deacetylase Inhibitors. ChemMedChem 2010, 5, 1232–1235 DOI: 10.1002/cmdc.201000087 Patil, V.; Guerrant, W.; Chen, P. C.; Gryder, B.; Benicewicz, D. B.; Khan, S. I.; Tekwani, B. L.; Oyelere, A. K. Antimalarial and Antileishmanial Activities of Histone Deacetylase (HDAC) Inhibitors with Triazole-Linked Cap Group. Bioorg. Med. Chem. 2010, 18, 415–425. DOI: 10.1016/j.bmc.2009.10.042 Dreaden, E. C.; Mwakwari, S. C.; Sodji, Q. H.; Oyelere, A. K.; El-Sayed, M. A. Tamoxifen−Poly(ethylene glycol)−Thiol Gold Nanoparticle Conjugates: Enhanced Potency and Selective Delivery for Breast Cancer Treatment. Bioconjugate Chem, 2009, 20, 2247–2253. DOI: 10.1021/bc9002212 Canzoneri, J. C.; Chen, P. C.; Oyelere, A. K. Design and Synthesis of Novel Histone Deacetylase Inhibitor Derived from Nuclear Localization Signal Peptide. Bioorg. Med. Chem. Lett. 2009, 19, 6588–6590.* Oyelere, A. K.; Chen, P. C.; Guerrant, W.; Mwakwari, S. C; Hood, R.; Zhang, Y.; Fan, Y. Nonpeptide Macrocyclic Histone Deacetylase (HDAC) Inhibitors. J. Med. Chem. 2009, 52, 456-468.* Canzoneri, J. C.; Oyelere, A. K. Interaction of Anthracyclines with Iron Responsive Element mRNAs. Nucleic Acids Res. 2008, 36, 6825–6834.*