Maria Pellegrini

Professor Pellegrini received her "laurea" degree in Chemistry in 1992, and Ph.D. in Chemistry in 1996, from the University of Padova, in Italy, working on conformational studies of bioactive cyclic peptides. She joined the group of Professor Dale F. Mierke as a post-doctoral fellow in 1996, first at Clark University and then at Brown University. In 1999 she moved to an industrial position at BASF and then Abbott Laboratories in Worcester MA. In 2002 she joined Biogen as a senior scientist where she utilized NMR spectroscopy for structural studies, screening efforts, and biophysical characterization of proteins. Prof. Pellegrini joined Dartmouth College in the summer of 2007.

Position: Research Assistant Professor of Chemistry
E-mail: Maria Pellegrini

Research Interests

Many processes in a living cell are regulated through the specific interaction between proteins. Targeting the disruption of protein-protein complexes for therapeutic purposes is considered a very attractive, albeit difficult, approach. In our research, we take advantage of information on the protein's overall fold, primary and secondary structure at the interface and flexibility to identify putative binding sites and design and test molecules that interfere with or block protein-protein interaction. We focus on peptides, peptidomimetics, and small molecular weight compounds.

Nuclear magnetic resonance (NMR) provides the unique advantage of allowing to investigate both protein structure and dynamics and has been effectively employed as a screening technique, especially in fragment-based approaches. We complement our NMR studies with a number of biophysical and biochemical techniques for characterization of proteins and binding interactions (EPR, CD, fluorescence, etc.) and with computational tools for structural refinement and model building.

Selected Publications

• Rushe M, Silvian L , Bixler S, Chen LL, Cheung A, Bowes S, Cuervo H, Berkowitz S, Zheng T, Guckian K, Pellegrini M, Lugovskoy A. "Structure of a NEMO/IKK-associating domain reveals architecture of the interaction site." Structure 2008 16:798-808
• Mierke DF, Mao L, Pellegrini M, Piserchio A, Plati J, Tsomaia N. "Structural characterization of the parathyroid hormone receptor domains determinant for ligand binding" Biochem. Soc. Trans. 2007 35:35721-3.
• Baker DP, Lin EY, Lin K, Pellegrini M, Petter RC, Chen LL, Arduini RM, Brickelmaier M, Wen D, Hess DM, Chen L, Grant D, Whitty A, Gill A, Lindner DJ, Pepinsky RB. "N-terminally PEGylated human interferon-beta-1a with improved pharmacokinetic properties and in vivo efficacy in a melanoma angiogenesis model." Bioconjug. Chem. 2006 17:179-88.
• Seck T, Pellegrini M, Florea AM, Grignoux V, Baron R, Mierke DF, Horne WC. "The delta e13 isoform of the calcitonin receptor forms a six-transmembrane domain receptor with dominant-negative effects on receptor surface expression and signaling." Mol. Endocrinol. 2005 19:2132-44.
• Cusack KP, Arnold LD, Barberis CE, Chen H, Ericsson AM, Gaza-Bulseco GS, Gordon TD, Grinnell CM, Harsch A, Pellegrini M, Tarcsa E. "A 13C NMR approach to categorizing potential limitations of alpha,beta-unsaturated carbonyl systems in drug-like molecules." Bioorg. Med. Chem. Lett. 2004 14:5503-7.
• Pellegrini M, Bremer AA, Ulfers AL, Boyd ND, Mierke DF. "Molecular characterization of the substance P/neurokinin-1 receptor complex: development of an experimentally based model." J. Biol. Chem. 2001 276:22862-7 .
• Pellegrini M, Liehr S, Fisher AL, Laub PB, Cooperman BS, Mierke DF. "Structure-based optimization of peptide inhibitors of mammalian ribonucleotide reductase." Biochemistry 2000 39:12210-5.
• Pellegrini M, Mierke DF. "Molecular complex of cholecystokinin-8 and N-terminus of the cholecystokinin A receptor by NMR spectroscopy." Biochemistry 1999 38:14775-83.
• Grant MA, Gentile LN, Shi QL, Pellegrini M, Hawrot E. "Expression and spectroscopic analysis of soluble nicotinic acetylcholine receptor fragments derived from the extracellular domain of the alpha-subunit" Biochemistry 1999 38:10730-42.
• Pellegrini M, Bisello A, Rosenblatt M, Chorev M, Mierke DF. "Binding domain of human parathyroid hormone receptor: from conformation to function." Biochemistry 1998 37:12737-43.