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ABSTRACT: Foldamers are sequence-specific oligomers akin to peptides, proteins and oligonucleotides that fold into well-defined three-dimensional structures. They offer the chemical biologist a broad pallet of building blocks for the construction of molecules that test and extend our understanding of protein folding and function. Foldamers also provide templates for presenting complex arrays of functional groups in virtually unlimited geometrical patterns, thereby presenting attractive opportunities for the design of molecules that bind in a sequence- and structure-specific manner to oligosaccharides, nucleic acids, membranes and proteins. We summarize recent advances and highlight the future applications and challenges of this rapidly expanding field.
Nature Chemical Biology 06/2007; 3(5):252-62. · 14.69 Impact Factor
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ABSTRACT: A family of nanoparticles featuring surfaces of varying hydrophobicity was synthesized. The efficiency of DNA-binding was determined, demonstrating in a fivefold modulation in binding a 37-mer DNA strand. Nanoparticle-binding causes a reversible conformational change in the DNA structure, as demonstrated by circular dichroism and fluorescence experiments. Furthermore, the affinity of the nanoparticle for the DNA can be regulated by external agents, though stability of the complex is observed at relatively high ionic strengths.
Chemical Biology & Drug Design 05/2006; 67(4):297-304. · 2.28 Impact Factor
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ABSTRACT: Positively-charged monolayer protected gold clusters (MMPCs) were mixed with sodium dodecyl sulfate (SDS). At lower SDS concentration, the initially water-soluble particles became organic-soluble while remaining discrete. Upon further addition of SDS, the particles aggregate and become water-soluble. NaCN decomposition, TEM, and DLS characterization reveal the morphology and properties of these encapsulated assemblies.
Colloids and Surfaces B Biointerfaces 01/2005; 39(3):119-23. · 3.46 Impact Factor
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ABSTRACT: Thioalkyl and thioalkylated oligo(ethylene glycol) (OEG) ligands with chain-end functionality were used to fabricate water-soluble CdSe nanoparticle scaffolds. Surface recognition of chymotrypsin (ChT) was achieved using these functionalized nanoparticle scaffolds, with three levels of interaction demonstrated: no interaction (OEG terminated with hydroxyl group), inhibition with denaturation (carboxylate-terminated thioalkyl ligands), and inhibition with retention of structure (carboxylate-terminated OEG). The latter process was reversible upon an increase in ionic strength, with essentially complete restoration of enzymatic activity.
Journal of the American Chemical Society 02/2004; 126(3):739-43. · 9.91 Impact Factor
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Angewandte Chemie International Edition 02/2004; 43(6):724-7. · 13.45 Impact Factor
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Angewandte Chemie International Edition 01/2004; 43(6):724 - 727. · 13.45 Impact Factor
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ABSTRACT: Fig. (1). To-scale schematic of 2 nm gold nanoparticles with an octanethiol monolayer and several potential biological targets: shown are a 20mer DNA duplex, α-chymotrypsin, and phenylalanine tRNA. The similarity in size of the MPC with the biomolecules provides additional surface area in binding, useful in generating high affinity scaffolds. Abstract: Monolayer-protected nanoparticles represent a new class of receptors, capable of high affinity, multivalent binding with biomolecules. Networks of self-optimizing bioactive substituents can be introduced via facile place-exchange of functionalized thiols, approximating the diversified topology of biological surfaces. Extension of these particles to model systems and in catalysis is described.
Mini-Reviews in Organic Chemistry 01/2004; 100. · 2.41 Impact Factor
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ABSTRACT: Anionically functionalized amphiphilic nanoparticles efficiently inhibit chymotrypsin through electrostatic binding followed by protein denaturation. We demonstrate the ability to disrupt this "irreversible" inhibition of chymotrypsin through modification of the nanoparticle surface using cationic surfactants. Up to 50% of original chymotrypsin activity is rescued upon long-chain surfactant addition. Dynamic light-scattering studies demonstrate that chymotrypsin is released from the nanoparticle surface. The conformation of the rescued chymotrypsin was characterized by fluorescence and fluorescence anisotropy, indicating that chymotrypsin regains a high degree of native structure upon surfactant addition.
Journal of the American Chemical Society 12/2003; 125(44):13387-91. · 9.91 Impact Factor
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ABSTRACT: The structure and properties of gold nanoparticles make them useful for a wide array of biological application. Toxicity, however, has been observed at high concentrations using these systems. MTT, hemolysis, and bacterial viability assays were used to explore differential toxicity among the cell types used, using 2 nm core particles. These studies show that cationic particles are moderately toxic, whereas anionic particles are quite nontoxic. Concentration-dependent lysis mediated by initial electrostatic binding was observed in dye release studies using lipid vesicles, providing the probable mechanism for observed toxicity with the cationic MMPCs.
Bioconjugate Chemistry 15(4):897-900. · 4.93 Impact Factor
