Label-free Ligand Screening Featured in C&E News
Researchers have designed a new small molecule probe that binds to a protein and emits a fluorescent signal only when a drug molecule displaces it (J. Am. Chem. Soc., DOI: 10.1021/ja301204z). The chemists hope that the probe will provide a simple, rapid method to screen drug candidates.
One of Our Recent Publications
Abstract:Supramolecular nanoassemblies, which are capable of binding and delivering either lipophilic small molecules or hydrophilic molecules, are of great interest. Concurrently binding and delivering this combination of molecules is cumbersome, because of the opposing supramolecular host requirements. We describe the development of a versatile nanoassembly system that is capable of binding and delivering both, a protein and a lipophilic small molecule, simultaneously inside the cells.
Gonzalez-Toro, D.; Ryu, J.-H.; Chacko, R.; Zhuang, J.; Thayumanavan, S. "Concurrent Binding and Delivery of Proteins and Lipophilic Small Molecules Using Polymeric Nanogels" J. Am. Chem. Soc. 2012, 134, In press
2012
Julie Reynolds won the Merck Index Award.
Avital Percher won Departmental Recognition Award.
Jen Wilcox won the Poster Awardatn the Undergrduate Research Symposium.
BODIPY-based Polymer Reported to Have Panchromatic Absorption Features
Four novel π-conjugated copolymers incorporating 4,4-difluoro-4-borata-3a-azonia-4a-aza-s-indacene (BODIPY) core as the “donor” and quinoxaline (Qx), 2,1,3-benzothiadiazole (BzT), N,N′-di(2′-ethyl)hexyl-3,4,7,8-naphthalenetetracarboxylic diimide (NDI), and N,N′-di(2′-ethyl)hexyl-3,4,9,10-perylene tetracarboxylic diimide (PDI) as acceptors were designed and synthesized via Sonogashira polymerization. The polymers were characterized by 1H NMR spectroscopy, gel permeation chromatography (GPC), UV–vis absorption spectroscopy, and cyclic voltammetry. Density functional theory (DFT) calculations were performed on polymer repeat units, and the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energy levels were estimated from the optimized geometry using B3LYP functional and 6-311g(d,p) basis set. Copolymers with Qx and BzT possessed HOMO and LUMO energy levels comparable to those of BODIPY homopolymer, while PDI stabilized both HOMO and LUMO levels. Semiconductor behavior of these polymers was estimated in organic thin-film transistors (OTFT). While the homopolymer, Qx, and BzT-based copolymers showed only p-type semiconductor behavior, copolymers with PDI and NDI showed only n-type behavior. See report in Macromolecules, 2011, 44, 47671,
Protein-binding Induced Disassembly Expanded to Lipophilic Ligands
Supramolecular nanoassemblies that respond to the presence of proteins are of great interest, as aberrations in protein concentrations represent the primary imbalances found in a diseased state. We present here a molecular design, syntheses, and study of facially amphiphilic dendrimers that respond to the presence of the protein, Immunoglobulin G. It is of particular interest that the ligand functionality, utilized for causing the binding-induced disassembly, be lipophilic. Demonstration of binding with lipophilic ligands greatly expands the repertoire of binding-induced disassembly, since this covers a rather large class of ligand moieties designed for proteins and these provide specific insights in to the mechanistic pathways that are available for the binding-induced disassembly process. In this paper, we describe the details of the binding induced disassembly, including the change in size of the assembly in response to proteins, concurrent release of non-covalently encapsulated guest molecules, and the specificity of the disassembly process. See report in Chem. Eur. J. 2012, 18, 223