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
Area(s) of Expertise
Bioorganic and Medicinal Chemistry
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.
In vivo imaging of patients using [I-123]-Altropane, an imaging agent using a technology developed in Prof. Hanson’s laboratory. The figure illustrates the localization of the radiotracer in normal brain, but decreased uptake in patients with moderate and severe Parkinsonism.
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.
The figure illustrates the proposed binding mode for 11β-substituted estradiol derivatives that function as antiestrogens. Synthesis of such compounds involves multistep transformations using organometallic reagents and coupling chemistry.
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.
The figure illustrates the strategy for preparing multifunctional nanoparticles as drug delivery systems in which we can selectively incorporate targeting, imaging and therapeutic modalities.
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.
Design and retrosynthesis of target proteomimetics
206 Hurtig Hall