Vincent M. Rotello

Professor of Chemistry, University of Massachusetts

Email: rotello@cisco.chem.umass.edu
V. Rotello Chemistry Dept Website

Ph.D.: Yale University
Postdoctoral Training: National Science Foundation Postdoctoral Fellow, Massachusetts Institute of Technology

Synthetic Models of Biomolecular Activity

Architecture, conformational energetics, and reactivity are the three determinants of activity in enzymes. Isolation and observation of these features individually are difficult or impossible due to the complexity of the native macromolecular systems. Our research uses synthetic organic chemistry to create model systems that allow in-depth study of individual aspects of biomolecular behavior. We are currently targeting two major aspects of molecular function: electron transfer in flavoenzymes and conformational energetics of α-helices.

Flavoenzymes (redox enzymes that use flavin co-factors) are involved in key reactions in aerobic metabolism, biotransformations, and detoxification of xenobiotics. One of the key requirements for their activity is the correct geometry between the flavin and substrate. In order to recreate this geometry in a model system, we have designed a modular flavin receptor. This molecule uses hydrogen bonding to provide a defined host-guest geometry. We are currently using these receptors to provide insight into the mechanisms of flavoenzyme activity.

The rigidity of current synthetic receptors limits their ability to mimic biological hosts such as enzymes and antibodies. In order to overcome this difficulty, we are creating a series of peptide-based molecular clefts. In these systems, the ability of peptide α-helices to undergo conformational adjustments will be used to create binding sites sufficiently flexible to allow effective modeling of biophysical properties. The clefts use both natural and unnatural amino acid sidechains to provide recognition elements for biologically interesting target molecules.

Representative publications:

Frankamp, B. L.; Fischer, N. O.; Hong, R.; Srivastava, S.; Rotello, V. M. “Surface Modification using Cubic Silsesquioxane Ligands. Facile Synthesis of Water-Soluble Metal Oxide Nanoparticles” Chem. Mat. , 2006 , 18 , 956-959.

Hong, R.; Han, G.; Kim, B.; Forbes, N. S.; Rotello, V. M.; “Glutathione-Mediated Drug Release using Monolayer Protected Nanoparticle Carriers” J. Am. Chem. Soc. , 2006 , 128 , 1078-1079.

Han, G.; Martin, C. M.; Rotello, V. M. “Stability of Gold Nanoparticle-Bound DNA towards Biological, Physical and Chemical Agents” Chem. Biol. Drug Des. , 2006 , 67 , 78-82.

Verma, A.; Srivastava, S.; Rotello, V. M. “Modulation of the Interparticle Spacing and Optical Behavior of Nanoparticle Ensembles using a Single Protein Spacer” Chem. Mat. 2005 , 17 , 6317-6322.

You, C.-C.; De, M.; Rotello, V. M. “Contrasting Effects of Exterior and Interior Hydrophobic Moieties in the Complexation of Amino Acid-Functionalized Gold Clusters with a-Chymotrypsin” Org Lett., 2005 , 7 , 5685-5687.

Shenhar, S.; Xu, H.; Frankamp, B. L.; Mates, T. E.; Sanyal, A.; Uzun, O.; Rotello, V. M. “Molecular Recognition in Structured Matrices: Control of Guest Localization in Block Copolymer Films” J. Am. Chem. Soc ., 2005 , 127 , 16318-16324.

You, C.-C. De, M.; Rotello, V. M. “Monolayer-Protected Nanoparticle-Protein Interactions” Curr. Opin. Chem. Biol., 2005 , 9 , 639-646.

Han, G.; Chari, N. S.; Verma, A.; Hong, R.; Martin, C. T.; Rotello, V. M. “Controlled Recovery of the Transcription of Nanoparticle-Bound DNA by Intracellular Concentrations of Glutathione" Bioconjugate Chem. 2005 , 16 , 1356-1359.

Xu, H.; Norsten, T. B.; Uzun, O.; Jeoung E.; Rotello, V. M. “Stimuli Responsive Surfaces through Recognition-Mediated Polymer Modification” Chem. Comm ., 2005 , 5157-5159.

Uzun, U.; Xu, H.; Jeoung, E.; Thibault, R. J.; Rotello, V. M. “Recognition-Induced Polymersomes: Structure and Mechanism of Formation” ” Chem. Eur. J., 2005 , 11 , 6916-6920.

Hong, R.; Fischer, N. O.; Emrick, T.; Rotello, V. M. “Surface PEGylation and Ligand Exchange Chemistry of FePt Nanoparticles for Biological Applications” Chem. Mat. , 2005 , 17 , 10693-10698.

Shenhar, R.; Jeoung, E.; Srivastava, S.; Norsten, T. B.; Rotello, V. M. “Cross-Linked Nanoparticle Stripes and Hexagonal Networks Obtained Via Selective Patterning of Block Copolymer Thin Films” Adv. Mat. , 2005 , 17 , 2206-2210.

You, C-C.; De, M.; Rotello, V. M. “Tunable Inhibition and Denaturation of a-Chymotrypsin with Amino Acid-Functionalized Gold Nanoparticles” J. Am. Chem. Soc ., 2005 , 127 , 12873-12881.

Carroll, J. B.; Cooke, G.; Garety, J. F.; Jordan, B. J.; Mabruk, S ; Rotello, V. M. “The Electrochemically-Tuneable Interactions Between Flavin-Functionalised C(60) Derivatives and 2,6-Diethylamidopyridine” Chem. Comm. 2005 , 3838-3840.

Sandaraj, B. S.; Vutukuri D. H.; Simard, J. M.; Khalikerd, A.; Hong, R.; Rotello, V. M.; Thayumanavan, S. “Non-Covalent Modification of Protein Surface using Amphiphilic Polymeric Scaffold – Implications in Modulating Protein Function” J. Am. Chem. Soc ., 2005 , 127 , 10693-10698.

Frankamp, B. L.; Boal, A. K.; Tuominen, M. T.; Rotello, V. M. “Direct Control of the Magnetic Interaction Between Superparamagnetic Nanoparticles Using Dendrimer Mediated Self-Assembly” J. Am. Chem. Soc ., 2005 , 127 , 9731-9735.

Nakade, H.; Ilker, M. F.; Uzun, O.; LaPointe, N. L.; Coughlin, E. B.; Rotello V. M. “Duplex Strand Formation using Alternating Copolymers” Chem. Comm. 2005 , 3271-3273.

Carroll, J. B.; Jordan, B. J.; Xu, H.; Erdogan,. B.; Lee, L.; Cheng, L.; Tiernan, C.; Cooke, G.; Rotello, Vincent M. “Model Systems for Flavoenzyme Activity: Site Isolated Redox Behavior in Flavin Functionalized Random Polystyrene Copolymers” Org. Lett. , 2005 , 7 , 10693-10698.

Simard, J. M.; Szymanski, B.; Rotello, V. M. “Control of Substrate Selectivity through Complexation and Release of Chymoptrypsin from Gold Nanoparticle Surfaces” J. Biomed. Nanotech ., 2005 , 1 , 341-344..

Boyd, A. S. F.; Carroll, J. B.; Cooke, G.; Garety, J. F.; Jordan, B. J.; Mabruk, S.; Rosair, G.; Rotello, V. M. "Model systems for Flavoenzyme Activity: a Tuneable Intramolecularly Hydrogen Bonded Flavin-Diamidopyridine Complex" Chem. Comm . 2005 , 2468-2470

McCusker, C.; Carroll, J. B.; Rotello, V. M. “Cationic Polyhedral Oligomeric Silsesquioxane (POSS) Units as Carriers for Drug Delivery Processes” Chem. Comm. , 2005 , 996-998.

Simard, J. M.; Szymanski, B.; Rotello, V. M. “Reversible Regulation of Chymotrypsin Activity using Negatively Charged Gold Nanoparticles featuring Malonic Acid Termini” Med. Chem ., 2005 , 1 , 153-158.

Shenhar, R.; Norsten, T. B.; Rotello, V. M. “Polymer-Mediated Nanoparticle Assembly: Structural Control and Applications” Adv. Mat ., 2005 , 17 , 657-669

Srivastava, S.; Frankamp, B. L.; Rotello, V. M. “Controlled Plasmon Resonance of Gold Nanoparticles Self-Assembled with PAMAM Dendrimers” Chem. Mat. 2005 , 17 , 487-490.

Foster, P.; Lahti, P.M.; Carroll, J. B.; Rotello, V. M. “Molecular Recognition In a Uradinyl-Functionalized Stable Radical” Chem. Comm. 2005 , 895-897.

Arviso, R.; Verma. A.; Rotello, V.M. “Biomacromolecule Surface Recognition Using Nanoparticle Receptors” Supramol. Chem . 2005 , 17 , 155-161.

Srivastava, S.; Verma, A.; Frankamp, B. L.; Rotello, V. M.; “Controlled Assembly of Protein-Nanoparticle Composites through Protein Surface Recognition” Adv. Mat . , 2005 , 617-621.

Verma, A.; Rotello, V.M. “Surface Recognition of Biomacromolecules Using Nanoparticle Receptors” Chem Comm ., 2005 , 301-312.

Greaves, M. and Rotello, V. (1997) Model Systems for Flavoenzyme Activity. Hydrogen Bond Recognition of FMN in a Sol-Gel Matrix. J. Am. Chem. Soc. 119, 10569-10572.

Breinlinger, E. and Rotello, V. (1997) Model Systems for Flavoenzyme Activity. Modulation of Flavin Redox Potentials Through Pi-stacking Interactions. J. Am. Chem. Soc. 119, 1165-1166.

Deans, R., Cooke, G. and Rotello, V. (1997) Model Systems for Flavoenzyme Activity. Regulation of Flavin Recognition via Modulation of Receptor Hydrogen Bond Donor-Acceptor Properties. J. Org. Chem. 62, 836-839.