The Molecular Foundry - Organic and Macromolecular Synthesis - Staff

Brett Helms

Staff Scientist, Organic and Macromolecular Synthesis Facility

Research interests

My research focuses on precision chemical synthesis, characterization and application of functional macromolecules and their assemblies. New materials enabling optoelectronic communication with living systems are being explored as well as applications of polymer-biomolecule hybrids.

Visit The Helms Research Group.

Current projects

Cytosolic Delivery of Protein-Coated Quantum Dots via Polymer-Mediated Endosomal Disruption
Efficient cytosolic delivery of quantum dots (QDs) into cells has been a persistent challenge to researchers using these exceptionally bright, photostable probes for bioimaging. We have developed novel polymer compositions and architectures that mediate the uptake of protein-coated quantum dots and subsequently facilitate their release from vesicular entrapment following internalization. We are currently exploring the size-dependent mechanism of delivery and the role of polymer surface chemistry on intracellular trafficking and processing.

Environment-Responsive Quantum Dot Biosensors
We are developing new ratiometric probes based on quantum dots for investigating various aspects of the chemical or physical environment within biological systems. We have pursued robust synthetic strategies for passivating quantum dots with biofriendly, responsive coatings based on (bio)polymers of interest that modulate their optical properties in a reversible manner.

Past Research

Reconstructing Multivalent Phage Binding with Dendrimer Peptide Hybrids
Multivalent interactions abound in biological systems. We have shown that targeting strategies based on multivalency can be particularly effective in enhancing the affinity and specificity of biomolecular interactions in a complex, heterogeneous context. Learn more

From phage display to dendrimer display. Phage display to collagen reveals a consensus binding sequence that is translated into a high affinity, versatile synthetic collagen-specific probe by mimicking the original pentavalent phage architecture on a dendritic wedge.
Bioinspired Catalytic Nanoreactors Using Dendritic and Other Macromolecular Architectures
We recently completed work with the Fréchet group at UC Berkeley and the Lippard group at MIT on a family of dendrimer catalysts that enable hydrocarbon oxidation using dioxygen. Hydrocarbon oxidation is relevant to several energy-related fields, from fine chemical production via catalysis to the manipulation of wasteful refinery burn-off into practical fuels. We were inspired by the family of enzymes known as the methane monooxygenases (e.g., sMMOH), which are responsible for the activation of methane at room temperature and pressure in methanotropic bacteria. A key feature of sMMOH translated into highly active dendrimer-based catalysts was its unique arrangement of two iron centers in a carboxylate rich environment that is sterically shielded by a hydrophobic pocket within the enzyme. Learn more

Hydrocarbon oxidation mediated by macromolecular catalysis inspired by proteins from methanotropic bacteria. Crystal structure of sMMOH and its unique non-heme bound diiron active site. This enzyme is known to oxidize small hydrocarbons under ambient conditions.

Selected publications

Lempens, E. H. M.; Helms, B. A.; Merkx, M.; Meijer, E. W. “Efficient and Chemoselective Surface Immobilization of Proteins by Using Aniline-Catalyzed Oxime Chemistry.” ChemBioChem 2009, 10, 658-662.
Helms, B.; van Baal, I.; Merkx, M.; Meijer, E. W. “Site-Specific Protein and Peptide Immobilization on a Biosensor Surface by Pulsed Native Chemical Ligation.” ChemBioChem 2007,8, 1790-1794.
Helms, B.; Meijer, E. W. “Dendrimers at Work.” Science 2006, 313, 929-930.
Helms, B.; Fréchet, J. M. J. “The Dendrimer Effect in Homogeneous Catalysis.” Adv. Syn. Catal. 2006, 348, 1125-1148.
Helms, B.; Guillaudeu, S. J; Xie, Y.; McMurdo, M.; Hawker, C. J. Fréchet, J. M. J. “One-Pot Reaction Cascades Using Star Polymers with Core-Confined Catalysts.” Angew. Chem. Int. Ed. 2005, 44, 6384-6387.

Education

Postdoc, Eindhoven University of Technology, with Prof. E. (Bert) W. Meijer

Ph.D., University of California, Berkeley, with Prof. Jean M. J. Fréchet

B.S., Harvey Mudd College

IBM Almaden Research Center (through CPIMA), under Craig Hawker