Bio-doped Nanocomposite Polymers:  Sol−Gel Bioencapsulates

Gill, Iqbal

doi:10.1021/cm0102483

Cited by 388 publications

(283 citation statements)

References 247 publications

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“…The best result was achieved by encapsulation of the enzyme in a sol-gel matrix derived from tetraethoxyorthosilicate (TEOS). [18] This approach resulted in a biocatalyst that revealed long-term activity when immobilised on the matrix.…”

Section: Introductionmentioning

confidence: 99%

Immobilisation of P450 BM‐3 and an NADP⁺ Cofactor Recycling System: Towards a Technical Application of Heme‐Containing Monooxygenases in Fine Chemical Synthesis

et al. 2003

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Cytochrome P450 monooxygenases are potentially a very useful class of hydroxylation catalysts; they are able to introduce oxygen at activated and nonactivated carbon-hydrogen bonds and thus lead to regio-and/or stereochemically pure compounds. However, this potential is lowered by their intrinsic low activity and inherent instability. P450-catalysed biotransformations require a constant supply of NAD(P)H, making the process an expensive one. To render these catalysts more suitable for industrial biocatalysis, the immobilisation of P450 BM-3 (CYP 102A1)from Bacillus megaterium in a sol-gel matrix was combined with a cofactor recycling system based on NADP + -dependent formate dehydrogenase (EC 1.2.1.2) fromPseudomonas sp. 101 and tested for practical applicability. This approach was used for the conversion of β-ionone, octane and naphthalene to the respective hydroxycompounds with DMSO as cosolvent using sol-gel immobilised P450 BM-3 mutants.

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Section: Introductionmentioning

confidence: 99%

Immobilisation of P450 BM‐3 and an NADP⁺ Cofactor Recycling System: Towards a Technical Application of Heme‐Containing Monooxygenases in Fine Chemical Synthesis

et al. 2003

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“…The first step toward construction of a viable MetaChip is the optimization of P450 catalysis in sol-gel arrays. Sol-gels offer important advantages for the fabrication of protein-based materials and biocatalytic devices because of their optical transparency, compatibility with various organic moieties, and stability in harsh environments (31)(32)(33). Furthermore, the porosity of sol-gels can be precisely controlled, as can the robustness of the sol-gel structure.…”

Section: Resultsmentioning

confidence: 99%

Metabolizing enzyme toxicology assay chip (MetaChip) for high-throughput microscale toxicity analyses

Lee

Park

Dordick

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

152

110

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The clinical progression of new chemical entities to pharmaceuticals remains hindered by the relatively slow pace of technology development in toxicology and clinical safety evaluation, particularly in vitro approaches, that can be used in the preclinical and early clinical phases of drug development. To alleviate this bottleneck, we have developed a metabolizing enzyme toxicology assay chip (MetaChip) that combines high-throughput P450 catalysis with cell-based screening on a microscale platform. The MetaChip concept is demonstrated by using sol-gel encapsulated P450s to activate the prodrug cyclophosphamide, which is the major constituent of the anticancer drug Cytoxan, as well as other compounds that are activated by P450 metabolism. The MetaChip provides a high-throughput microscale alternative to currently used in vitro methods for human metabolism and toxicology screening based on liver slices, cultured human hepatocytes, purified microsomal preparations, or isolated and purified P450s. This technology creates opportunities for rapid and inexpensive assessment of ADME͞Tox (absorption, distribution, metabolism, excretion͞toxicology) at very early phases of drug development, thereby enabling unsuitable candidates to be eliminated from consideration much earlier in the drug discovery process.in situ drug metabolism ͉ in vitro cytotoxicity ͉ P450 ͉ sol-gel encapsulation I n the past decade, there has been a dramatic increase in the number of new chemical entities (NCEs) and screenable drug targets as a result of combinatorial chemistry and advances in genomics and proteomics (1-4). Nevertheless, these advances have not translated into an increased number of new drug approvals (5, 6), in part because of the high failure rate due to toxicity of the NCE or its metabolite(s) (7). Furthermore, screening for toxicity at early stages of the drug discovery process is precluded by the large number of compounds available at the lead discovery stage, forcing medicinal chemists to select compounds for lead optimization based on limited information about their toxicological properties. In particular, there remains a lack of in vitro techniques that can adequately mimic human metabolism and therefore assess cell-specific toxicity of NCEs and their metabolites at speeds consistent with high-throughput biological activity screening.The human body, primarily the liver, contains a variety of enzymes that are involved in the metabolism of the myriad chemicals that comprise today's pharmaceuticals. By far the most important class of metabolic enzymes is the cytochromes P450, which are directly involved in the initial (or ''first-pass'') clearance of drugs from the body (8, 9). During this process, drug metabolites are generated, some of which are biologically active in their own right and exert the desired pharmacological effect. For example, conversion of the antihistamine loratadine to descarboethoxyloratadine by CYP2D6 and CYP3A4 is required for biological activity (10). Often, however, drug metabolism can lead to undesirable ...

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“…32,39 Both optical-and electrochemical-sensing schemes have been demonstrated, involving a variety of matrices based on sol-gel synthesis. Sol-gel-based biosensors have been reported for a wide variety of oxidoreductases.…”

Section: Figurementioning

confidence: 99%

Molecules in Glass: Probes, Ordered Assemblies, and Functional Materials

Dunn

Zink

2007

Acc. Chem. Res.

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Research on the properties and applications of molecules doped into sol-gel-derived silica matrices has expanded rapidly. This Account begins with a brief review of the use of the dopant molecules as probes of the changes that occur as the system evolves from the initial sol to the final xerogel during the formation of monoliths, thin films, and mesostructured films. Methods of deliberately placing desired molecules in specific regions of the mesostructure are discussed, and an application, energy transfer, is presented. Finally, encapsulation of biological molecules is examined, and two important aspects, stabilization of the biomolecules and applications as biosensors, are described.

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Bio-doped Nanocomposite Polymers: Sol−Gel Bioencapsulates

Cited by 388 publications

References 247 publications

Immobilisation of P450 BM‐3 and an NADP⁺ Cofactor Recycling System: Towards a Technical Application of Heme‐Containing Monooxygenases in Fine Chemical Synthesis

Immobilisation of P450 BM‐3 and an NADP⁺ Cofactor Recycling System: Towards a Technical Application of Heme‐Containing Monooxygenases in Fine Chemical Synthesis

Metabolizing enzyme toxicology assay chip (MetaChip) for high-throughput microscale toxicity analyses

Molecules in Glass: Probes, Ordered Assemblies, and Functional Materials

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Bio-doped Nanocomposite Polymers: Sol−Gel Bioencapsulates

Cited by 388 publications

References 247 publications

Immobilisation of P450 BM‐3 and an NADP+ Cofactor Recycling System: Towards a Technical Application of Heme‐Containing Monooxygenases in Fine Chemical Synthesis

Immobilisation of P450 BM‐3 and an NADP+ Cofactor Recycling System: Towards a Technical Application of Heme‐Containing Monooxygenases in Fine Chemical Synthesis

Metabolizing enzyme toxicology assay chip (MetaChip) for high-throughput microscale toxicity analyses

Molecules in Glass: Probes, Ordered Assemblies, and Functional Materials

Contact Info

Product

Resources

About

Immobilisation of P450 BM‐3 and an NADP⁺ Cofactor Recycling System: Towards a Technical Application of Heme‐Containing Monooxygenases in Fine Chemical Synthesis

Immobilisation of P450 BM‐3 and an NADP⁺ Cofactor Recycling System: Towards a Technical Application of Heme‐Containing Monooxygenases in Fine Chemical Synthesis