Search results for: Gabriele Varani

Items from 1 to 20 out of 73 results

article

Effect of glycerol on the physical and mechanical properties of thin gellan gum films for oral drug delivery

Patrizia Paolicelli, Stefania Petralito, Gabriele Varani, Martina Nardoni, more

International Journal of Pharmaceutics > 2018 > 547 > 1-2 > 226-234

In this work, deacylated gellan gum and the plasticizer glycerol were used as primary components for the preparation of thin films intended for the oral delivery of therapeutic molecules. The samples were prepared by a solvent casting method and characterized for their thickness, tensile properties, swelling ability, mucoadhesion capacity and uniform drug distribution. The amount of glycerol was varied...

article

DESIGN AND CHARACTERIZATION OF A BIOCOMPATIBLE PHYSICAL HYDROGEL BASED ON SCLEROGLUCAN FOR TOPICAL DRUG DELIVERY

Patrizia Paolicelli, Gabriele Varani, Settimio Pacelli, Elisa Ogliani, more

Carbohydrate Polymers > 2017 > 174 > C > 960-969

Physical hydrogels of a high-carboxymethylated derivative of scleroglucan (Scl-CM₃₀₀) were investigated as potential systems for topical drug delivery using three different therapeutic molecules (fluconazole, diclofenac and betamethasone).Rheological tests were carried out on drug-loaded hydrogels along with in-vitro release studies in a vertical Franz cell, in order to investigate if and how different...

article

Applications of NMR to structure determination of RNAs large and small

Ravi P. Barnwal, Fan Yang, Gabriele Varani

Archives of Biochemistry and Biophysics > 2017 > 628 > C > 42-56

Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool to investigate the structure and dynamics of RNA, because many biologically important RNAs have conformationally flexible structures, which makes them difficult to crystallize. Functional, independently folded RNA domains, range in size between simple stem-loops of as few as 10–20 nucleotides, to 50–70 nucleotides, the size of tRNA and...

article

Targeting Influenza A Virus RNA Promoter

Angel Bottini, Surya K. De, Bainan Wu, Changyan Tang, more

Chemical Biology & Drug Design > 86 > 4 > 663 - 673

The emergence of drug‐resistant strains of influenza virus makes exploring new classes of inhibitors that target universally conserved viral targets a highly important goal. The influenza A viral genome is made up of eight single‐stranded RNA‐negative segments. The RNA promoter, consisting of the conserved sequences at the 3′ and 5′ end of each RNA genomic segment, is universally conserved among influenza...

article

Structure based approaches for targeting non-coding RNAs with small molecules

Matthew D Shortridge, Gabriele Varani

Current Opinion in Structural Biology > 2015 > 30 > Complete > 79-88

The increasing appreciation of the central role of non-coding RNAs (miRNAs and long non-coding RNAs) in chronic and degenerative human disease makes them attractive therapeutic targets. This would not be unprecedented: the bacterial ribosomal RNA is a mainstay for antibacterial treatment, while the conservation and functional importance of viral RNA regulatory elements has long suggested they would...

article

Rtr1 Is a Dual Specificity Phosphatase That Dephosphorylates Tyr1 and Ser5 on the RNA Polymerase II CTD

Peter L. Hsu, Fan Yang, Whitney Smith-Kinnaman, Wen Yang, more

Journal of Molecular Biology > 2014 > 426 > 16 > 2970-2981

The phosphorylation state of heptapeptide repeats within the C-terminal domain (CTD) of the largest subunit of RNA polymerase II (PolII) controls the transcription cycle and is maintained by the competing action of kinases and phosphatases. Rtr1 was recently proposed to be the enzyme responsible for the transition of PolII into the elongation and termination phases of transcription by removing the...

article

Engineering RNA‐binding proteins for biology

Yu Chen, Gabriele Varani

The FEBS Journal > 280 > 16 > 3734 - 3754

RNA‐binding proteins play essential roles in the regulation of gene expression. Many have modular structures and combine relatively few common domains in various arrangements to recognize RNA sequences and/or structures. Recent progress in engineering the specificity of the PUF class RNA‐binding proteins has shown that RNA‐binding domains may be combined with various effector or functional domains...

article

Preparation of RNA samples with narrow line widths for solid state NMR investigations

Wei Huang, Michael F. Bardaro, Gabriele Varani, Gary P. Drobny

Journal of Magnetic Resonance > 2012 > 223 > Complete > 51-54

Solid state NMR can provide detailed structural and dynamic information on biological systems that cannot be studied under solution conditions, and can investigate motions which occur with rates that cannot be fully studied by solution NMR. This approach has successfully been used to study proteins, but the application of multidimensional solid state NMR to RNA has been limited because reported line...

article

Independent alignment of RNA for dynamic studies using residual dipolar couplings

Michael F. Bardaro, Gabriele Varani

Journal of Biomolecular NMR > 2012 > 54 > 1 > 69-80

Molecular motion and dynamics play an essential role in the biological function of many RNAs. An important source of information on biomolecular motion can be found in residual dipolar couplings which contain dynamics information over the entire ms-ps timescale. However, these methods are not fully applicable to RNA because nucleic acid molecules tend to align in a highly collinear manner in different...

article

GFT projection NMR for efficient ¹H/¹³C sugar spin system identification in nucleic acids

Hanudatta S. Atreya, Bharathwaj Sathyamoorthy, Garima Jaipuria, Victor Beaumont, more

Journal of Biomolecular NMR > 2012 > 54 > 4 > 337-342

A newly implemented G-matrix Fourier transform (GFT) (4,3)D HC(C)CH experiment is presented in conjunction with (4,3)D HCCH to efficiently identify ¹H/¹³C sugar spin systems in ¹³C labeled nucleic acids. This experiment enables rapid collection of highly resolved relay 4D HC(C)CH spectral information, that is, shift correlations of ¹³C–¹H groups separated by two carbon bonds. For RNA, (4,3)D HC(C)CH...

article

Theory of Nonrigid Rotational Motion Applied to NMR Relaxation in RNA

Prashant S. Emani, Gregory L. Olsen, Gabriele Varani, Gary P. Drobny

The Journal of Physical Chemistry A > 2011 > 115 > 44 > 12055 - 12069

article

Structural genomics of infectious disease drug targets: the SSGCID

Robin Stacy, Darren W. Begley, Isabelle Phan, Bart L. Staker, more

Acta Crystallographica Section F > 67 > 9 > 979 - 984

The Seattle Structural Genomics Center for Infectious Disease (SSGCID) is a consortium of researchers at Seattle BioMed, Emerald BioStructures, the University of Washington and Pacific Northwest National Laboratory that was established to apply structural genomics approaches to drug targets from infectious disease organisms. The SSGCID is currently funded over a five‐year period by the National Institute...

article

Comparative analysis of glutaredoxin domains from bacterial opportunistic pathogens

Thomas Leeper, Suxin Zhang, Wesley C. Van Voorhis, Peter J. Myler, more

Acta Crystallographica Section F > 67 > 9 > 1141 - 1147

Glutaredoxin proteins (GLXRs) are essential components of the glutathione system that reductively detoxify substances such as arsenic and peroxides and are important in the synthesis of DNA via ribonucleotide reductases. NMR solution structures of glutaredoxin domains from two Gram‐negative opportunistic pathogens, Brucella melitensis and Bartonella henselae, are presented. These domains lack the...

article

Finding the Missing Code of RNA Recognition by PUF Proteins

Yu Chen, Gabriele Varani

Chemistry & Biology > 2011 > 18 > 7 > 821-823

Pumilio and FBF homology (PUF) proteins represent highly promising candidates for engineering sequence-specific RNA recognition, but were only known to recognize G, A, and U, significantly limiting applications. Two groups (Filipovska et al., 2011; Dong et al., 2011) have now reported the discovery of the cytosine-recognition code for PUF proteins.

article

A Small-Molecule Probe Induces a Conformation in HIV TAR RNA Capable of Binding Drug-Like Fragments

Amy Davidson, Darren W. Begley, Carmen Lau, Gabriele Varani

Journal of Molecular Biology > 2011 > 410 > 5 > 984-996

The HIV-1 transactivation response (TAR) element–Tat interaction is a potentially valuable target for treating HIV infection, but efforts to develop TAR-binding antiviral drugs have not yet yielded a successful candidate for clinical development. In this work, we describe a novel approach toward screening fragments against RNA that uses a chemical probe to target the Tat-binding region of TAR. This...

article

Interactions of protein side chains with RNA defined with REDOR solid state NMR

Wei Huang, Gabriele Varani, Gary P. Drobny

Journal of Biomolecular NMR > 2011 > 51 > 3 > 347-356

Formation of the complex between human immunodeficiency virus type-1 Tat protein and the transactivation response region (TAR) RNA is vital for transcriptional elongation, yet the structure of the Tat-TAR complex remains to be established. The NMR structures of free TAR, and TAR bound to Tat-derived peptides have been obtained by solution NMR, but only a small number of intermolecular NOEs could be...

article

¹³ C/ ¹⁵ N− ¹⁹ F Intermolecular REDOR NMR Study of the Interaction of TAR RNA with Tat Peptides

Wei Huang, Gabriele Varani, Gary P. Drobny

Journal of the American Chemical Society > 2010 > 132 > 50 > 17643 - 17645

article

Slow Exchange Model of Nonrigid Rotational Motion in RNA for Combined Solid-State and Solution NMR Studies

Prashant S. Emani, Gregory L. Olsen, Dorothy C. Echodu, Gabriele Varani, more

The Journal of Physical Chemistry B > 2010 > 114 > 48 > 15991 - 16002

article

Novel Protein–Protein Contacts Facilitate mRNA 3′-Processing Signal Recognition by Rna15 and Hrp1

Thomas C. Leeper, Xiangping Qu, Connie Lu, Claire Moore, more

Journal of Molecular Biology > 2010 > 401 > 3 > 334-349

Precise 3′-end processing of mRNA is essential for correct gene expression, yet in yeast, 3′-processing signals consist of multiple ambiguous sequence elements. Two neighboring elements upstream of the cleavage site are particularly important for the accuracy (positioning element) and efficiency (efficiency element) of 3′-processing and are recognized by the RNA-binding proteins Rna15 and Hrp1, respectively...

article

Fragment‐based discovery of novel thymidylate synthase leads by NMR screening and group epitope mapping

Darren W. Begley, Suxin Zheng, Gabriele Varani

Chemical Biology & Drug Design > 76 > 3 > 218 - 233

Solution‐state nuclear magnetic resonance (NMR) is a versatile tool for the study of binding interactions between small molecules and macromolecular targets. We applied ligand‐based NMR techniques to the study of human thymidylate synthase (hTS) using known nanomolar inhibitors and a library of small molecule fragments. Screening by NMR led to the rapid identification of ligand pairs that bind in...

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Search results for: Gabriele Varani

Effect of glycerol on the physical and mechanical properties of thin gellan gum films for oral drug delivery

DESIGN AND CHARACTERIZATION OF A BIOCOMPATIBLE PHYSICAL HYDROGEL BASED ON SCLEROGLUCAN FOR TOPICAL DRUG DELIVERY

Applications of NMR to structure determination of RNAs large and small

Targeting Influenza A Virus RNA Promoter

Structure based approaches for targeting non-coding RNAs with small molecules

Rtr1 Is a Dual Specificity Phosphatase That Dephosphorylates Tyr1 and Ser5 on the RNA Polymerase II CTD

Engineering RNA‐binding proteins for biology

Preparation of RNA samples with narrow line widths for solid state NMR investigations

Independent alignment of RNA for dynamic studies using residual dipolar couplings

GFT projection NMR for efficient ¹H/¹³C sugar spin system identification in nucleic acids

Theory of Nonrigid Rotational Motion Applied to NMR Relaxation in RNA

Structural genomics of infectious disease drug targets: the SSGCID

Comparative analysis of glutaredoxin domains from bacterial opportunistic pathogens

Finding the Missing Code of RNA Recognition by PUF Proteins

A Small-Molecule Probe Induces a Conformation in HIV TAR RNA Capable of Binding Drug-Like Fragments

Interactions of protein side chains with RNA defined with REDOR solid state NMR

¹³ C/ ¹⁵ N− ¹⁹ F Intermolecular REDOR NMR Study of the Interaction of TAR RNA with Tat Peptides

Slow Exchange Model of Nonrigid Rotational Motion in RNA for Combined Solid-State and Solution NMR Studies

Novel Protein–Protein Contacts Facilitate mRNA 3′-Processing Signal Recognition by Rna15 and Hrp1

Fragment‐based discovery of novel thymidylate synthase leads by NMR screening and group epitope mapping

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