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Contact Information

Office: Room 351

Labs: Rooms 344 and 346

Chemistry Biochemistry Building
P.O. Box 173400
Bozeman, MT 59717

Phone: 406-994-3051

Fax: 406-994-5407

Email: mcloninger@montana.edu

Research Group Website

 

Education

  • B.S.: 1991 Texas Christian University, Fort Worth, TX
  • Ph.D.: 1996 University of Wisconsin-Madison
  • Postdoc.: 1996-1997 University of Wisconsin Enzyme Institute (with Prof. Perry Frey)
  • Postdoc.: 1997-1999 University of California-Irvine (with Prof. Larry Overman)

Courses

  • CHMY 333 HONORS ORGANIC CHEMISTRY II
  • CHMY 533 PHYSICAL ORGANIC CHEMISTRY

Awards and Professional Activities:

  • 2011 Kopriva Faculty Lectureship in Interdisciplinary Biomedical Sciences (MSU)
  • 2010 Cox Family Faculty Excellence Award (MSU)
  • 2009 Provost’s Award for Undergraduate Research/Creativity Mentoring (MSU)
  • 2008 Charles & Nora L. Wiley Award for Meritorious Research (MSU)
  • 2001 and 2002: Undergraduate Chemistry Society Chemistry Professor of the Year
  • 2001 NSF CAREER Award
  • 1997-1999 California President's Postdoctoral Fellowship

Cloninger Group Overview

My research program is based on key questions in chemical biology. How do cells 'talk' to one another? What are the signaling mechanisms that are used to control cell functions? What processes mediate the adhesions and metastatic migrations of cancer cells?
One way to study these complex natural processes is to build and evaluate simpler model systems. Our approach is to synthesize synthetic multivalent frameworks for the study cellular recognition events.

Keywords:

Bioinorganic, Chemical Biology, Organic, Spectroscopy, Synthesis

Using dendrimers to study cancer metastasis

Many reports suggest that cell surface carbohydrates serve a critical function in malignant transformation and metastasis. We are developing artificial carbohydrate arrays to mimic and interfere with metastasis. Our goal is to advance fundamental knowledge regarding the role of protein-carbohydrate and carbohydrate-carbohydrate interactions in the metastatic spread of cancer. Concurrently, new therapeutic agents to arrest cancer metastasis may also emerge.

Keywords:

Biochemistry, Bioinorganic, Chemical Biology, Organic

Dendrimer characterization

fig. 4

The evaluation of dendrimer properties is another area of macromolecular chemistry that is of interest to us. To study the relative locations and the dynamic nature of dendrimer endgroups, we have functionalized dendrimers with varying amounts of spin-labels. EPR spectra of TEMPO-labeled G(4)-PAMAM dendrimers (Figure 4) suggest that termini are randomly distributed on heterogeneously-functionalized dendrimers. Additional EPR studies with other generations of dendrimers and with non-random surface spin-labeling distributions are underway.

Keywords:

Chemical Biology, Organic, Spectroscopy, Structure, Synthesis

Using dendrimers to study multivalent protein-carbohydrate interactions

fig 1

We are using dendrimers (macromolecules consisting of a series of branches around an inner core) to study the interaction of carbohydrates with receptor proteins called lectins. Although a wide variety of biological processes including fertilization, development, and the mounting of an immune response rely on protein-carbohydrate interactions for cellular recognition and adhesion (Figure 1), these interactions are not well understood. Because the affinity of lectins for individual saccharide units is relatively weak, the adhesion of lectins to saccharides on the surface of a cell involves multipoint attachment (multivalency).

fig 2

We are using saccharide-functionalized poly(amidoamine) (PAMAM) dendrimers (Figure 2) to learn more about multivalency in protein carbohydrate interactions. Dendrimers are ideal frameworks for the study of how systematic structural changes alter the way that a glycopolymer interacts with a protein. In addition to changing the dendrimer generation, the degree of carbohydrate loading on a dendrimer can also be readily changed by controlling the number of equivalents of sugar residues that are added to the dendrimer (Figure 3). We can systematically and predictably attenuate the relative affinities of the dendrimers for the lectins by incorporating low and high affinity ligands into the dendrimer. We can also influence how many proteins bind to each dendrimer. We're evaluating the comparative activity of these dendrimers for lectins such as Concanavalin A, Pisum Sativum, and Cyanovirin N using a variety of assays. In this way, we are learning about the factors that control physiologically relevant multivalent protein-carbohydrate interactions. Because of their ready tunability, the carbohydrate functionalized dendrimers described here should provide guidelines for the development of synthetic multivalent frameworks for many applications in chemical biology

fig 3

Keywords:

Biochemistry, Chemical Biology, Organic

Recent Publications

Goodman, C. K.; Wolfenden, M. L.; Nangia-Makker, P.; Michel, A. K.; Raz, A.; Cloninger, M. J. “Multivalent scaffolds induce galectin-3 aggregation into nanoparticles.” Beilstein J. Org. Chem. 2014, 10, 1570-1577

Michel, A. K.; Nangia-Makker, P.; Raz, A.; Cloninger, M. J. “Lactose-functionalized dendrimers arbitrate the interaction of galectin-3/MUC1 mediated cancer cellular aggregation.” ChemBioChem, 2014, 15, 2106-2112.

Ennist, J. H.; Gobrogge, E. A.; Schlick, K. H.; Walker, R. A.; Cloninger, M. J. "Cyclodextrin-Functionalized Chromatographic Materials Tailored for Reversible Adsorption." ACS Appl. Mater. Interfaces 2014, articles ASAP. DOI: 10.1021/am504975y

Michel, A. K.; Mattson, A.; Cloninger, M. J. “Using Indium(III) as a Promoter for Glycosylation.” Carbohydr. Res. 2012, 347, 142-146.

Cloninger, M. J. "Biological Applications of Dendrimers" Curr. Op. Chem. Biol. 2002, 6, 742-748.

 
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