Simon H. Friedman

Bio: Simon H. Friedman is an academic researcher from University of Missouri–Kansas City. The author has contributed to research in topics: RNA interference & RNA. The author has an hindex of 15, co-authored 38 publications receiving 1929 citations. Previous affiliations of Simon H. Friedman include University of Missouri.

Inhibition of the HIV-1 protease by fullerene derivatives: model building studies and experimental verification

Abstract: The ability of C[sub 60] fullerene ([open quotes]Bucky Ball[close quotes]) derivatives to interact with the active site of HIV-1 protease (HIVP) has been examined through model building and simple physical chemical analysis. The model complexes generated via the program DOCK3 suggest that C[sub 60] derivatives will fit snugly in the active site, thereby removing 298 A[sup 2] of primarily nonpolar surface from solvent exposure and driving ligand/protein association. The prediction that these compounds should bind to the active site and thereby act as inhibitors has been borne out by the experimental evidence. Kinetic analysis of HIVP in the presence of a water-soluble C[sub 60] derivative, bis(phenethylamino-succinate) C[sub 60], suggests a competitive mode of inhibition. This is consistent with and supports the predicted binding mode. Diamino C[sub 60] has been proposed as a [open quotes]second-generation[close quotes] C[sub 60] derivative that will be able to form salt bridges with the catalytic aspartic acids in addition to Van der Waals contacts with the nonpolar HIVP surface, thereby improving the binding relative to the tested compound. 15 refs., 6 figs., 1 tab.

Synthesis of a fullerene derivative for the inhibition of HIV enzymes

Abstract: A diamido diacid diphenyl fulleroid derivative was designed specifically to inhibit an HIV enzyme. The detailed synthesis and mass spectrometric analysis of the water-soluble, biologically active methanofullerene are described. The compound was prepared in three steps from C[sub 60] via a suitably diphenyldiazomethane. High-resolution mass spectrometric analysis was possible only under mild matrix-assisted laser desorption/ionization Fourier transform mass spectrometry conditions. Direct infrared or ultraviolet laser desorption resulted exclusively in observation of C[sub 60] ions, in either positive or negative mode. 13 refs., 3 figs.

Patterning of Gene Expression Using New Photolabile Groups Applied to Light Activated RNAi

Abstract: The spacing, timing, and amount of gene expression are crucial for a range of biological processes, including development. For this reason, there have been many attempts to bring gene expression under the control of light. We have previously shown that RNA interference (RNAi) can be controlled with light through the use of siRNA and dsRNA that have their terminal phosphates modified with the dimethoxy nitro phenyl ethyl (DMNPE) group. Upon irradiation, these groups photolyze and release native RNA. The main problem with light activated RNA interference (LARI) to date is that the groups used only partially block RNA interference prior to irradiation, thus limiting the utility of the approach. Here, we describe a new photocleavable group, cyclo-dodecyl DMNPE (CD-DMNPE), designed to completely block the interaction of duplexes with the cellular machinery responsible for RNA interference prior to irradiation. This allowed us to switch from normal to a near complete reduction in gene expression using light, and to construct well-defined patterns of gene expression in cell monolayers. Because this approach is built on the RNA interference pathway, it benefits from the ability to quickly identify duplexes that are effective at low or subnanomolar concentrations. In addition, it allows for the targeting of endogenous genes without additional genetic manipulation. Finally, because of the regiospecificity of CD-DMNPE, it allows a standard duplex to be quickly modified in a single step. The combination of its efficacy and ease of application will allow for the facile control of the spacing, timing, and degree of gene expression in a range of biological systems.

Light-activated RNA interference using double-stranded siRNA precursors modified using a remarkable regiospecificity of diazo-based photolabile groups

Abstract: Diazo-based precursors of photolabile groups have been used extensively for modifying nucleic acids, with the intention of toggling biological processes with light. These processes include transcription, translation and RNA interference. In these cases, the photolabile groups have been typically depicted as modifying the phosphate backbone of RNA and DNA. In this work we find that these diazo-based reagents in fact react very poorly with backbone phosphates. Instead, they show a remarkable specificity for terminal phosphates and very modest modification of the nucleobases. Furthermore, the photo deprotection of these terminal modifications is shown to be much more facile than nucleobase modified sites. In this study we have characterized this regiospecificity using RNA duplexes and model nucleotides, analyzed using LC/MS/MS. We have also applied this understanding of the regio-specificity to our technique of light activated RNA interference (LARI). We examined 27-mer double-stranded precursors of siRNA (‘dsRNA’), and have modified them using the photo-cleavable di-methoxy nitro phenyl ethyl group (DMNPE) group. By incorporating terminal phosphates in the dsRNA, we are able to guide DMNPE to react at these terminal locations. These modified dsRNA duplexes show superior performance to our previously described DMNPE-modified siRNA, with the range of expression that can be toggled by light increasing by a factor of two.

Photochemical Reactions as Key Steps in Organic Synthesis

Abstract: 2.3. [4 + 4] Cycloadditions 1058 2.4. Photocycloadditions of Aromatic Compounds 1058 2.4.1. Benzene Derivatives 1058 2.4.2. Condensed Aromatic Compounds 1060 3. Photochemical Rearrangements 1061 4. Cyclizations 1064 4.1. Pericyclizations 1064 4.2. Norrish−Yang Reaction 1066 5. Photochemical Extrusion of Small Molecules 1067 6. Photochemical Electron Transfer 1068 6.1. Photochemical Electron-Transfer Reactions with a Catalytic Sensitizer 1068

Biologically active molecules with a "light switch".

Abstract: Biologically active compounds which are light-responsive offer experimental possibilities which are otherwise very difficult to achieve. Since light can be manipulated very precisely, for example, with lasers and microscopes rapid jumps in concentration of the active form of molecules are possible with exact control of the area, time, and dosage. The development of such strategies started in the 1970s. This review summarizes new developments of the last five years and deals with "small molecules", proteins, and nucleic acids which can either be irreversibly activated with light (these compounds are referred to as "caged compounds") or reversibly switched between an active and an inactive state.

Chemical modifications and bioconjugate reactions of nanomaterials for sensing, imaging, drug delivery and therapy.

Abstract: As prepared nanomaterials of metals, semiconductors, polymers and carbon often need surface modifications such as ligand exchange, and chemical and bioconjugate reactions for various biosensor, bioanalytical, bioimaging, drug delivery and therapeutic applications. Such surface modifications help us to control the physico-chemical, toxicological and pharmacological properties of nanomaterials. Furthermore, introduction of various reactive functional groups on the surface of nanomaterials allows us to conjugate a spectrum of contrast agents, antibodies, peptides, ligands, drugs and genes, and construct multifunctional and hybrid nanomaterials for the targeted imaging and treatment of cancers. This tutorial review is intended to provide an introduction to newcomers about how chemical and bioconjugate reactions transform the surface of nanomaterials such as silica nanoparticles, gold nanoparticles, gold quantum clusters, semiconductor quantum dots, carbon nanotubes, fullerene and graphene, and accordingly formulate them for applications such as biosensing, bioimaging, drug and gene delivery, chemotherapy, photodynamic therapy and photothermal therapy. Nonetheless, controversial reports and our growing concerns about toxicity and pharmacokinetics of nanomaterials suggest the need for not only rigorous in vivo experiments in animal models but also novel nanomaterials for practical applications in the clinical settings. Further reading of original and review articles cited herein is necessary to buildup in-depth knowledge about the chemistry, bioconjugate chemistry and biological applications of individual nanomaterials.

The era of carbon allotropes

Abstract: Twenty-five years on from the discovery of C60, the outstanding properties and potential applications of the synthetic carbon allotropes — fullerenes, nanotubes and graphene — overwhelmingly illustrate their unique scientific and technological importance.