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WIREs Nanomed Nanobiotechnol
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Nanoparticle‐based biologic mimetics

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Abstract Centered on solid chemistry foundations, biology and materials science have reached a crossroad where bottom‐up designs of new biologically important nanomaterials are a reality. The topics discussed here present the interdisciplinary field of creating biological mimics. Specifically, this discussion focuses on mimics that are developed using various types of metal nanoparticles (particularly gold) through facile synthetic methods. These methods conjugate biologically relevant molecules, e.g., small molecules, peptides, proteins, and carbohydrates, in conformationally favorable orientations on the particle surface. These new products provide stable, safe, and effective substitutes for working with potentially hazardous biologicals for applications such as drug targeting, immunological studies, biosensor development, and biocatalysis. Many standard bioanalytical techniques can be used to characterize and validate the efficacy of these new materials, including quartz crystal microbalance (QCM), surface plasmon resonance (SPR), and enzyme‐linked immunosorbent assay (ELISA). Metal nanoparticle–based biomimetics continue to be developed as potential replacements for the native biomolecule in applications of immunoassays and catalysis. Copyright © 2008 John Wiley & Sons, Inc. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

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Comparison of the glutathione (a) and tiopronin (b) ligands used to functionalize MPCs. Tiopronin is a truncated form of the 3‐amino acid glutathione, with overlap shown in red. (Reprinted, with permission, from Ref. 62. Copyright 2005 American Chemical Society.).

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The quartz crystal microbalance (QCM) biosensor showing an antibody recognizing a functionalized nanoparticle (antigen mimic). (Reprinted, with permission, Wiley Periodicals, Inc.).

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The noncovalent interaction based place‐exchange reaction. (Reprinted, with permission, Wiley Periodicals, Inc.).

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Chart of the different rates at which place exchange and (possibly) migration occur. (Reprinted, with permission, from Ref. 33. Copyright 1999 American Chemical Society.).

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Scheme of the thiol place‐exchange reaction. The stoichiometry of the incoming to exiting ligand is 1:1.

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Examples of thiolate ligands used in the synthesis of water‐soluble Au monolayer‐protected clusters (MPCs). (a) tiopronin, (b) glutathione, (c) 4‐mercaptobenzoic acid, (d) 1‐thio‐β‐D‐glucose, (e) N, N, N‐trimethyl (mercaptoundecyl)ammonium (TMA).

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Modified Brust reaction scheme for polar ligands.

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Hydroxy‐ and imidazole‐functionalized nanoparticles working together to catalyze silica formation. The ligands used to functionalize the particles are shown in (a), while the interaction between particles in (b) and (c). Part (d) shows the stepwise synthetic route of the ligands. (Reprinted, with permission, Wiley Periodicals, Inc.).

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Model of Au55 clusters irreversibly bound to the grooves of DNA. (Reprinted, with permission, Wiley Periodicals, Inc.).

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Loop presenting MPCs (left) shown compared to the native protein (middle) and the linear presenting monolayer‐protected cluster (MPC) (right). (Reprinted, with permission, Wiley Periodicals, Inc.).

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Step‐by‐step creation of the conformational mimic nanoparticle using the synthetic protective antigen (PA) peptide.

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Different nanostructures used: (a) the 3‐D GSH‐MPC, (b) the 3‐D 10‐amino acid hemagglutinin monolayer‐protected clusters (HA‐MPC), and (c) the same 10‐amino acid sequence for HA as a 2‐D self‐assembled monolayer (SAM) with tiopronin spacers. (Reprinted, with permission, from Ref. 63. Copyright 2005 American Chemical Society.).

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