Robert N. Hanson
206 Hurtig Hall
Bioorganic and Medicinal Chemistry
1973-5 Postdoctoral -Department of Medicinal
Chemistry, University of Minnesota, Minneapolis, MN
1973 Ph.D. University of California, Berkeley
1968 B.A. Augsburg College, Minneapolis, Minnesota
Development of Novel Radiotracers and Radiopharmaceuticals.The Hanson group developed the method for radiohalogenation via trialkylstannyl precursors. This method, first used in 1980 is the current standard for introducing most radiohalogens and radiocarbon groups onto aromatic compounds. The research group continues to develop methods for rapid labeling and purification of radiotracers and for preparing novel precursors for such labeling studies. Current areas of interest include growth factor receptor tyrosine kinase inhibitors, conventional and unconventional steroid hormone agonists and antagonists, and functionalized gold and iron oxide nanoparticles.
Development of Novel Steroid Hormone Receptor Ligands.Our interest in steroidal derivatives represents over 30 years of studies related to breast cancer research. The objectives include the development of diagnostic agents for the detection and evaluation of the disease, therapeutic agents for the treatment of the disease, and biochemical probes for understanding the disease. Within this broad program, we are exploring the effect of substitution at the 17α-position of estradiol to determine the extent to which the receptor can undergo protein remodeling. Another specific aim is to identify radiofluorinated derivatives that can be used for Positron Emission Mammography (PEM) of the breast. To develop better anti-estrogenic agents, we are exploring the introduction of additional biologically active groups at the 11β-position. Such materials would have two therapeutic effects that may act synergistically. We are also exploring whether the substituent effects observed in our studies with the estrogen receptor can be extended to other steroid hormone receptors, such as the androgen, progestin and glucocorticoid receptors.
Targeted drug delivery using multifunctional multivalent nanoparticles.Our research has developed a novel strategy for preparing multifunctional nanoparticles as a targeted drug delivery platform. Our approach utilizes our background in synthetic medicinal chemistry to prepare a variety of bifunctional chemo-orthogonal linkers which can be used to modify both the nanoparticle surface and a series of targeting, imaging, and therapeutic groups. Our selective convergent ligation methods then can systematically generate the multifunctional nanoparticles that can locate and treat specific tumor cells.
Proteomimetics.A new area of research in the Hanson group involves the design and synthesis of α-helical proteomimetics. Such materials display functional groups present in helical peptides but lack any central resemblance to a peptide core. The project involves identification of biological targets for which there is a helical peptide binding partner and the rational design of a 2- or 3-twist proteomimetics using computational methods. Our approach involves the preparation of a series of functionalized components that can be assembled using metal-catalyzed coupling reactions to give the final compounds. Biological evaluation by our collaborators provides the basis for iterative revision of the hypothesis, redesign and resynthesis.
External SupportDepartment of Defense-Breast and Prostate Cancer Research Programs (BCRP/PCRP)
National Institutes of Health
Susan G Komen Foundation
Massachusetts Technology Transfer Center
Department of Energy-Office of Biological and Environmental Research
Hanson, Robert N., Biomedical Imaging- Advances in Radiotracer and Radiopharmaceutical Chemistry, in "Biomedical Imaging. The Chemistry of Labels, Probes and Contrast Agents," edited by Martin Braddock, RSC Publishing, Cambridge, UK (2010).
Hanson, Robert N. Steroidal anti-hormone hybrids with quinone antibiotics as antitumor agents. PCT Int. Appl. (2010), 101pp. CODEN: PIXXD2 WO 2010085747 A1 20100729.
Williams, Anna B.; Weiser, Patrick T.; Hanson, Robert N.; Gunther, Jillian R.; Katzenellenbogen, John A. Synthesis of Biphenyl Proteomimetics as Estrogen Receptor-α Coactivator Binding Inhibitors. Organic Letters (2009), 11(23), 5370-5373.
Hanson, Robert N. Modulators of nuclear receptor co-regulatory protein binding. PCT Int. Appl. (2009), 92pp. CODEN: PIXXD2 WO 2009117739 A1 20090924.
Hanson, Robert N.; Friel, Carolyn; Lee, Choon Young. Steroidal antiestrogens and antiandrogens and uses thereof. U.S. Pat. Appl. Publ. (2008), 57pp., Cont.-in-part of U.S. Ser. No. 369,582. CODEN: USXXCO US 2008166301 A1 20080710.
Nettles, Kendall W.; Bruning, John B.; Gil, German; O'Neill, Erin E.; Nowak, Jason; Hughs, Alun; Kim, Younchang; DeSombre, Eugene R.; Dilis, Robert; Hanson, Robert N.; Joachimiak, Andrzej; Greene, Geoffrey L. Structural plasticity in the oestrogen receptor ligand-binding domain. EMBO Reports (2007), 8(6), 563-568.
Hanson, Robert N.; Tongcharoensirikul, Pakamas; Dilis, Robert; Hughes, Alun; DeSombre, Eugene R. Synthesis and Evaluation of Isomeric (17α ,20E)-11β -Methoxy-21-(trifluoromethylphenyl)-19-norpregna-1,3,5(10),20-tetraene-3,17β -diols as ERa -Hormone Binding Domain Ligands: Effect of the Methoxy Group on Receptor Binding and Uterotrophic Growth. Journal of Medicinal Chemistry (2007), 50(3), 472-479.