Administration & Faculty
Aleksandar Todorovic, DPharm, PhD
Post-Graduate Instructor
Academic Fellow
503-352-7362
Education
2006 Doctor of Philosophy,
Medicinal Chemistry,
University of Florida,
Gainesville, Florida
2001 Dipl.Pharm.
University of Belgrade,
Faculty of Pharmacy,
Belgrade, Serbia
Areas of Research & Specialization
- The melanocortin system consists of five melanocortin receptors (MC1R-MC5R), melanocortin agonists that are processed from proopiomelanocortin prohormone (POMC) and, uniquely, two naturally occurring antagonists: agouti and agouti related protein (AGRP). Melanocortin ligands that are processed from POMC include alpha-Melanocyte Stimulating Hormone (a-MSH), beta-MSH, gamma-MSH and Adrenocorticotropic hormone (ACTH). Common structural feature to all melanocortin agonists, the tetrapeptide sequence His-Phe-Arg-Trp, is postulated to be important structural requirement necessary for eliciting pharmacological response at MC1R, MC3R, MC4R and MC5R. The role of melanocortin system in regulating pigmentation, coloration, energy homeostasis, obesity, exocrine gland function, among many, is noteworthy. My research related to melanocortin system involved the design, synthesis, and analytical characterization of novel peptides, peptide-mimetics and small molecules. The goal of my graduate education was focused on the design and discovery of melanocortin ligands (agonists or antagonists) with increased potency, selectivity and unique receptor pharmacology.
- Proteins in nature are produced in the process known as translation. This highly regulated process is controlled by multiple factors, known as initiation factors (IF). In eukaryotes, the complete mechanism of translation initiation is not fully elucidated as it involves at least 12 initiation factors. In bacteria, or prokaryotes, this mechanism is less complex and well defined. My goal is to better understand how translation initiation occurs in eukaryotes and how some specific factors contribute to it. Specifically, I am interested in the non canonical form of translation initiation that requires only 2 initiation factors and specific form of RNA that is highly structured at 5’ end, also known as internal ribosome entry site RNA (IRES). I was directly involved in characterization of human eukaryotic initiation factor 3 (eIF3) that consists of 13 non identical subunits with molecular weight of 800 kDa. Our limiting yields of eIF3 from HeLa cells prompted us to investigate new ways of expressing eIF3 in different systems (E.Coli) and trying to reconstitute minimal active sequence in regard to translation initiation via its binding to human 40S ribosomal subunit or hepatitis C virus internal entry site RNA (IRES).
Publications (* indicates first co-author)
Todorovic A, Karljikovic-Rajic K, Agbaba D, Vukicevic- Nikolic D, Riley TN, Different Approaches in Pharmaceutical Education: Comparison of Three Educational Models, Pharm.Ed., 2 209-212 (2002)
Todorovic A, Holder JR, Scott JW, Haskell- Luevano C,
Synthesis and activity of the melanocortin Xaa-d-Phe-Arg-Trp-NH tetrapeptides with amide bond modifications, J.Pep. Res., 63, 270-278 (2004)
Irani BG, Holder JR, Todorovic A, Wilczynski AM, Joseph CG, Wilson KR, Haskell-Luevano C,
Progress in the development of melanocortin receptor selective ligands, Curr. Pharm. Des., 10, 3443-3479 (2004)
Haskell-Luevano C, Todorovic A, Gridley K, Sorenson N, Irani B, Xiang Z,
The melanocortin pathway: effects of voluntary exercise on the melanocortin-4 receptor knockout mice and ACTH(1-24) ligand structure activity relationships at the melanocortin-2 receptor, Endocr. Res., 30, 591-597 (2004)
Todorovic A, Holder JR, Bauzo RM, Scott JW, Haskell- Luevano C, Long chain fatty acid (LCFA) N-acyl derivatives of melanocortin X-His-DPhe-Arg-Trp-NH2 tetrapeptides: potency and selectivity alteration at mMCR system, Peptide Revolution: Genomic, Proteomics & Therapeutics, Proceeding of the 18th American Peptide Symposium, (Chorev M. and Sawyer TK, Editors), Kluwer Academic Publishers, the Netherlands, 641-642, (2004)
Todorovic A, Holder JR, Bauzo RM, Scott JW, Kavanagh R, Abdel-Malek Z, Haskell- Luevano C,
N-terminal fatty acylated His-dPhe-Arg-Trp-NH(2) tetrapeptides: influence of fatty acid chain length on potency and selectivity at the mouse melanocortin receptors and human melanocytes, J. Med. Chem., 48, 3328-3336 (2005)
Todorovic A and Haskell- Luevano C,
A review of melanocortin receptor small molecule ligands, Peptides, 26, 2026-2036 (2005)
Irani BG, Holder JR, Todorovic A, Wilczynski AM, Joseph CG, Wilson KR, Haskell-Luevano C, Development of melanocortin receptor selective ligands, Front Med. Chem., 3, 285-334 (2006)
Abdel-Malek ZA, Kadekaro AL, Kavanagh RJ, Todorovic A, Koikov LN, McNulty JC, Jackson PJ, Millhauser GL, Schwemberger S, Babcock G, Haskell-Luevano C, Knittel JJ,
Melanoma prevention strategy based on using tetrapeptide alpha-MSH analogs that protect human melanocytes from UV-induced DNA damage and cytotoxicity, FASEB J., 20, 1561-1563 (2006)
Wilson KR, Todorovic A, Proneth B amd Haskell-Luevano C,
Overview of endogenous and synthetic melanocortin peptides, Cell. Mol. Biol.,52, issue 2, 3-20 (2006)
Todorovic A, Joseph CG, Sorensen NB, Wood MS and Haskell-Luevano C,
Structure-activity relationships of melanocortin agonists containing the benzimidazole scaffold. Chem. Bio. Drug Des. 69 (5),338-349 (2007)
Cai Q, Todorovic A*, Andaya A, Gao J, Leary JA and Cate JHD, Distinct regions of human eIF3 are sufficient for binding to the HCV IRES and the 40S ribosomal subunit. J. Mol. Biol. 403, 185-196 (2010)
Sun C, Todorovic A*, Audi JQ, Bai Y, Villa N, Snyder M, Aschyan J, Lewis CS, Hartland A, Gradia S, Fraser CS, Doudna JA, Nogales E and Cate JHD Functional reconstitution of human eukaryotic translation initiation factor 3 (eIF3), Proc. Natl. Acad. Sci. U.S.A. 108 (51), 20473-20478 (2011)
Jäger S, Cimermancic P, Gulbahce N, Johnson JR, McGovern KE, Clarke SC, Shales M, Mercenne G, Pache L, Li K, Hernandez H, Jang GM, Roth SL, Akiva E, Marlett J, Stephens M, D'Orso I, Fernandes J, Fahey M, Mahon C, O'Donoghue AJ, Todorovic A, Morris JH, Maltby DA, Alber T, Cagney G, Bushman FD, Young JA, Chanda SK, Sundquist WI, Kortemme T, Hernandez RD, Craik CS, Burlingame A, Sali A, Frankel AD, Krogan NJ,
Global landscape of HIV-human protein complexes, Nature doi: 10.1038/nature10719. (2011)