Name: Michael Braden Title: Research Assistant Professor Email: michael.braden@umontana.edu Phone: 406 243-6069 Office: SB 482

Background

Michael Braden received his B.S. in Biochemistry from the University of Oregon in 1999. From 1997-2001 he worked at Marker Gene Technologies in Eugene, Oregon as a research assistant in synthetic organic chemistry and molecular biology. Following this, Michael pursued his graduate degree in medicinal chemistry and molecular pharmacology at Purdue University under the mentoring of Dr. David Nichols. Michael was awarded his Ph.D. in 2007 and moved to the University of Montana for a post-doctoral fellowship under Dr. John Gerdes. Michael was promoted to research assistant professor within the Department of Biomedical and Pharmaceutical Sciences in 2010.

Research Statement

Research in the Braden lab connects computational chemistry, molecular pharmacology, and medicinal chemistry of central nervous system (CNS) targets and their ligands, including neurotransmitter transporters and G-protein coupled receptors. Computational modeling of protein target structures and ligand-docking simulations provide hypotheses for ligand development and structural biology evaluations. Novel ligands are synthesized and pharmacologically evaluated within our laboratory. The effects of site-directed mutagenesis on CNS target protein structure and function are also performed and evaluated within our laboratory. These novel ligands and structural evaluations help to further refine our computational models as well as develop robust small molecule libraries of potential therapeutics, research tools, and diagnostic probes. Ligands with ideal properties are assessed as diagnostic probes in vivo through collaboration with other laboratories at the University of Montana as well as extramural. For example, novel ligands are developed specifically for positron emission tomography (PET) of CNS targets. PET imaging affords a unique opportunity to dynamically probe target protein densities in near-real time. In addition to supporting ligand development for CNS PET agents, our laboratory is also well trained in analysis and interpretation of PET experimental results.

Publications

Guo L, Suarez AI, Braden MR, Gerdes JM, Thompson CM, Inhibition of acetylcholinesterase by chromophore-linked fluorophosphonates Bioorg Med Chem Lett. 2010 Feb 1;20(3):1194-7.

Braden MR and Nichols DE, Assessment of the roles of Serines 5.43(239) and 5.46(242) for binding and potency of agonist ligands at the human serotonin 5-HT2A receptor Molec. Pharm. 72(5):1200-9.

US Patent 12/077898: Gerdes JM, Bolstad DB, Braden MR, and Barany A. 1-[(2-substituted)-Piperazin-1-yl]-isoquinolines as Norepinephrine Transporter Inhibitor Agents as Antidepressants and Positron Emission Tomography Imaging Agents. 2008.

Braden MR, Parrish JC, Naylor JC and Nichols DE, Molecular interaction of serotonin 5-HT2A receptor residues Phe339 (6.51) and Phe340(6.52) with super potent N-benzyl phenethylamine agonists Molec. Pharm. 2006, 70:1956-64.

McLean TH, Parrish JC, Braden MR, Marona-Lewicka D and Nichols DE,
1-Aminomethylbenzocyclo-alkanes: conformationally-restricted hallucinogenic phenethylamine analogues as functionallyselective 5-HT2A receptor agonists J Med Chem 2006, 49:5794-5803.

McLean TH, Chambers JJ, Parrish JC, Braden MR, Marona-Lewicka D, Kurrasch-Orbaugh DM and Nichols DE, C-(4,5,6-trimethoxyindan-1-yl)-methanamine: a mescaline analogue designed using a homology model of the 5-HT2A receptor J Med Chem 2006, 49:4269-74.

Parrish JC, Braden MR, Gundy E, and Nichols DE, Differential Phospholipase C Activation by Phenylalkylamine Serotonin 5-HT2A Receptor Agonists J. Neurochem. 2005, 95:1575-84.

Naleway JJ, Howard-Till RA, Guzikowski AP, Schutte RC, Braden MR, Fox, BA, Bashey, G, Pinhiero, N and Mehrotra, R, Marker Gene Directed Drug-Delivery to Recombinant Tumor Cells FASEB J., 2000, 14(8) A1410.

Guzikowski AP, Shipp C, Howard RA, Schutte RC, Braden MR and Naleway JJ Cyclic Peptidase Substrates for Fluorescent Analysis of Caspase 3 Enzyme Activity (2000) Proc. SPIE 3913:54-63.