Kinetics and thermodynamics of BI-BII interconversion altered by T:G mismatches in DNA.

T:G mismatches in DNA result in humans primarily from deamination of methylated CpG sites. They are repaired by redundant systems, such as thymine DNA glycosylase (TDG) and methyl-binding domain enzyme (MBD4), and maintenance of these sites has been implicated in epigenetic processes. The process by which these enzymes identify a canonical DNA base in the incorrect basepairing context remains a mystery. However, the conserved contacts of the repair enzymes with the DNA backbone suggests a role for protein-phosphate interaction in the recognition and repair processes. We have used 31P NMR to investigate the energetics of DNA backbone BI-BII interconversion, and for this work have focused on alterations to the activation barriers to interconversion and the effect of a mismatch compared with canonical DNA. We have found that alterations to the ΔG of interconversion for T:G basepairs are remarkably similar to U:G basepairs in the form of stepwise differences in ΔG of 1-2 kcal/mol greater than equivalent steps in unmodified DNA, suggesting a universality of this result for TDG substrates. Likewise, we see perturbations to the free energy (∼1 kcal/mol) and enthalpy (2-5 kcal/mol) of activation for the BI-BII interconversion localized to the phosphates flanking the mismatch. Overall our results strongly suggest that the perturbed backbone energetics in T:G basepairs play a significant role in the recognition process of DNA repair enzymes.

Fluorine (19F) Nuclear Magnetic Resonance Spectroscopy For Real Time Maraviroc Analysis From Microparticulate Systems.

Real time analysis of pharmaceuticals in controlled release nano and microsystems remains a challenge. It is hypothesized that fluorine 19 nuclear magnetic resonance (19F qNMR) can be used for real time quantification and in vitro release of maraviroc (MVC). The release of maraviroc was analyzed in simulated body fluids from spray dried sodium alginate microspheres (MS) using the 19F qNMR method. Calibration produced a linearity curve in concentration range (0.42 mg/ml - 15 mg/ml), and the limits of detection and quantification values were 0.97 mg/ml and 2.93 mg/ml, respectively. The method was confirmed to be specific, accurate, precise, and robust (%RSE > 2%). MVC was successfully microencapsulated (18% w/w) as evidenced by the FT-IR spectra and SEM images. The MS had an average diameter of 2.522 ± 0.15 µm, with a zeta potential of - 61.31 ± 2.1 mV. Overall, the 19F qNMR method enabled a direct and real time quantification of MVC for an efficient drug release kinetics. This approach could be potentially used to quantify fluorinated drug potency, purity, and stability, and evaluate in vitro release kinetic from different formulations.

Investigation on the Promoter-Induced Rapid Non-Aqueous Media Synthesis of SAPO-35 and Methanol-to-Olefin Reaction.

Microporous SAPO-35 molecular sieves (Levyne type) were synthesized in non-aqueous media by using different inorganic promoters (HClO4 -, HF, H3PO4, and NaNO3) to enhance the rate of crystallization, and the as-synthesized materials were characterized by using different methods such as powder X-ray diffraction spectroscopy (PXRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), magic angle spinning-nuclear magnetic resonance spectroscopy (MAS-NMR), Brunauer-Emmett-Teller (BET) analysis, and X-ray photoelectron spectroscopy (XPS). From PXRD patterns, it was found that all the materials have a highly crystalline nature without any other impurities. SEM images reveal rhombohedral particles in all synthesis conditions. The framework structure of the synthesized materials was identified by FT-IR spectroscopy, and it reveals that all materials gave a similar framework structure. From BET and XPS, we have confirmed that the pore size and pore diameters along with the elemental compositions have a minor change. The 27Al, 31P, and 29Si MAS-NMR spectra of all the promoter-based SAPO-35 materials are close to those of the standard SAPO-35 material. All the above characterization studies reveal the formation of SAPO-35 in a short time with promoters. The catalytic application studies of these synthesized materials for a methanol-to-olefin conversion reaction were performed, and the efficiency of these materials was found to be similar to that of standard materials.

Direct and Real-Time Quantification Of Bortezomib Release From Alginate Microparticles Using Boron (11B) Nuclear Magnetic Resonance Spectroscopy.

This study developed and validated a solution-state quantitative boron nuclear magnetic resonance (11B qNMR) method for the real-time quantification of boron containing bioactive agents with emerging therapeutic applications. Hence, this study may offer an alternative analytic method to estimate drug potency, purity, stability, or in vitro release kinetics of boron-containing pharmaceutical formulations/compounds, especially in cases where dialysis is typically required but limited. The 11B qNMR method was linear in the range tested, and the detection and quantification limits were 1.87 and 5.65 mM, respectively. The method was also specific, accurate, precise, and robust (%RSE < 2%). The 11B qNMR method was applied to the in vitro release study of a model drug, bortezomib (BTZ), from alginate microparticles, and results were compared to the traditional dialysis method. The alginate microparticles were prepared by spray drying, and the mean particle diameter was 2.36 ± 0.19 µm with a polydispersity index (PDI) of 0.253. The microparticles surface charge density was -57.1 ± 2.2 mV. More than 20% difference in the total amount of BTZ released from the microparticle formulation was observed between the direct 11B qNMR and dialysis methods. Furthermore, the dialysis method was not suitable to determine the initial burst release of BTZ from the microparticles. Throughout the release study, the dialysis method consistently underestimated the level of drug released, probably due to the separating membrane that can interfere with the real-time drug transport process. Overall, compared to the dialysis method, the direct 11B qNMR method was accurate and provided a direct and real-time quantification of BTZ for an effective study of drug release kinetics.

Layer-by-Layer Engineered Microbicide Drug Delivery System Targeting HIV-1 gp120: Physicochemical and Biological Properties.

The purpose of this study was to engineer a model anti-HIV microbicide (tenofovir) drug delivery system targeting HIV-1 envelope glycoprotein gp120 (HIV-1 g120) for the prevention of HIV sexual transmission. HIV-1 g120 and mannose responsive particles (MRP) were prepared through the layer-by-layer coating of calcium carbonate (CaCO3) with concanavalin A (Con A) and glycogen. MRP average particle size ranged from 881.7 ± 15.45 nm to 1130 ± 15.72 nm, depending on the number of Con A layers. Tenofovir encapsulation efficiency in CaCO3 was 74.4% with drug loading of 16.3% (w/w). MRP was non-cytotoxic to Lactobacillus crispatus, human vaginal keratinocytes (VK2), and murine macrophage RAW 264.7 cells and did not induce any significant proinflammatory nitric oxide release. Overall, compared to control, no statistically significant increase in proinflammatory cytokine IL-1α, IL-1ß, IL-6, MKC, IL-7, and interferon-γ-inducible protein 10 (IP10) levels was observed. Drug release profiles in the presence of methyl α-d-mannopyranoside and recombinant HIV-1 envelope glycoprotein gp120 followed Hixson-Crowell and Hopfenberg kinetic models, indicative of a surface-eroding system. The one Con A layer containing system was found to be the most sensitive (∼2-fold increase in drug release vs control SFS:VFS) at the lowest HIV gp120 concentration tested (25 µg/mL). Percent mucoadhesion, tested ex vivo on porcine vaginal tissue, ranged from 10% to 21%, depending on the number of Con A layers in the formulation. Collectively, these data suggested that the proposed HIV-1 g120 targeting, using MRP, potentially represent a safe and effective template for vaginal microbicide drug delivery, if future preclinical studies are conclusive.

Real-Time Analysis of Tenofovir Release Kinetics Using Quantitative Phosphorus (31P) Nuclear Magnetic Resonance Spectroscopy.

The dialysis method is classically used for drug separation before analysis, but does not provide direct and real-time drug quantification and has limitations affecting the dialysis rate. In this study, a phosphorus nuclear magnetic resonance (31P-qNMR) method is developed for the real-time quantification of therapeutic molecules in vitro. The release kinetics of model drug, tenofovir (anti-HIV microbicide), was analyzed in vaginal fluid simulant (VFS), seminal fluid simulant (SFS), and human plasma (HP) from chitosan nanofibers (size ∼100-200 nm) using the NMR (direct) method and compared with dialysis/UV-Vis (indirect) method. The assay was linear in VFS/SFS (0.20-5.0 mM), HP (0.30-5.0 mM of drug concentration range) and specific no drug 31P-qNMR chemical shift [∼15 ppm] interference with formulation/media components. Limit of detection values were 0.075/0.10/0.20 mM, whereas limit of quantification values were 0.20/0.20/0.30 mM in VFS/SFS/HP, respectively. The method was robust, precise (%RSE <2%), and accurate (%mean recovery 90%-110%). After 12 h, ∼77%/72%/70% wt/wt of tenofovir release was observed with direct, compared to ∼47%/52%/52% wt/wt by indirect method in VFS/SFS/HP, respectively. Approximately 20% decrease in %drug release observed with dialysis method suggested an interference with drug transport process due to the dialysis membrane and the Gibbs-Donnan effect. Overall, 31P-qNMR provides more accurate, real-time, and direct drug quantification for effective in vitro-in vivo correlation.

Spray-Dried Thiolated Chitosan-Coated Sodium Alginate Multilayer Microparticles for Vaginal HIV Microbicide Delivery.

It is hypothesized that novel thiolated chitosan-coated multilayer microparticles (MPs) with enhanced drug loading are more mucoadhesive than uncoated MPs and safe in vivo for vaginal delivery of topical anti-HIV microbicide. Formulation optimization is achieved through a custom experimental design and the alginate (AG) MPs cores are prepared using the spray drying method. The optimal MPs are then coated with the thiolated chitosan (TCS) using a layer-by-layer method. The morphological analysis, in situ drug payload, in vitro drug release profile, and mucoadhesion potential of the MPs are carried out using scanning electron microscopy, solid-state 31P NMR spectroscopy, UV spectroscopy, fluorescence imaging and periodic acid Schiff method, respectively. The cytotoxicity and preclinical safety of MPs are assessed on human vaginal (VK2/E6E7) and endocervical (End1/E6E7) epithelial cell lines and in female C57BL/6 mice, respectively. The results show that the MPs are successfully formulated with an average diameter ranging from 2 to 3 µm with a drug loading of 7-12% w/w. The drug release profile of these MPs primarily follows the Baker-Lonsdale and Korsmeyer-Peppas models. The MPs exhibit high mucoadhesion (20-50 folds) compared to native AGMPs. The multilayer MPs are noncytotoxic. Histological and immunochemical analysis of the mice genital tract shows neither signs of damage nor inflammatory cell infiltrate. These data highlight the potential use of TCS-coated AG-based multilayer MPs templates for the topical vaginal delivery of anti-HIV/AIDS microbicides.

A Novel Green TiO2 Photocatalyst with a Surface Charge-Transfer Complex of Ti and Hydrazine Groups.

The optical property of TiO2 plays an important role in its various and promising photocatalytic applications. Previous efforts in improving its optical properties include doping with various metal and/or non-metal elements, coupling with other colorful semiconductors or molecules, and hydrogenating to crystalline/disordered core/shell nanostructures. Here, we report a beautiful green TiO2 achieved by forming the charge-transfer complex of colorless hydrazine groups and surface Ti4+ , which extends the optical absorption into the near infrared region (≈1100 nm, 1.05 eV). It shows an enhanced photocatalytic performance in hydrogen generation under simulated sunlight, and degradation of organic pollution under visible light due to an impurity state (about 0.28 eV) resulting in fast electron-hole separation and injection of electrons from the ligand to the conduction band of TiO2 . This study demonstrates an alternative approach to tune the optical, impurity state and photocatalytic properties of TiO2 nanoparticles and we believe this will spur a wide interest in related materials and applications.

Tenofovir Containing Thiolated Chitosan Core/Shell Nanofibers: In Vitro and in Vivo Evaluations.

It is hypothesized that thiolated chitosan (TCS) core/shell nanofibers (NFs) can enhance the drug loading of tenofovir, a model low molecular weight and highly water-soluble drug molecule, and improve its mucoadhesivity and in vivo safety. To test this hypothesis, poly(ethylene oxide) (PEO) core with TCS and polylactic acid (PLA) shell NFs are fabricated by a coaxial electrospinning technique. The morphology, drug loading, drug release profiles, cytotoxicity and mucoadhesion of the NFs are analyzed using scanning and transmission electron microscopies, liquid chromatography, cytotoxicity assays on VK2/E6E7 and End1/E6E7 cell lines and Lactobacilli crispatus, fluorescence imaging and periodic acid colorimetric method, respectively. In vivo safety studies are performed in C57BL/6 mice followed by H&E and immunohistochemical (CD45) staining analysis of genital tract. The mean diameters of PEO, PEO/TCS, and PEO/TCS-PLA NFs are 118.56, 9.95, and 99.53 nm, respectively. The NFs exhibit smooth surface. The drug loading (13%-25%, w/w) increased by 10-fold compared to a nanoparticle formulation due to the application of the electrospinning technique. The NFs are noncytotoxic at the concentration of 1 mg/mL. The PEO/TCS-PLA core/shell NFs mostly exhibit a release kinetic following Weibull model (r2 = 0.9914), indicating the drug release from a matrix system. The core/shell NFs are 40-60-fold more bioadhesive than the pure PEO based NFs. The NFs are nontoxic and noninflammatory in vivo after daily treatment for up to 7 days. Owing to their enhanced drug loading and preliminary safety profile, the TCS core/shell NFs are promising candidates for the topical delivery of HIV/AIDS microbicides such as tenofovir.

Strong microwave absorption of hydrogenated wide bandgap semiconductor nanoparticles.

Electromagnetic interactions in the microelectronvolt (µeV) or microwave region have numerous important applications in both civil and military fields, such as electronic communications, signal protection, and antireflective coatings on airplanes against microwave detection. Traditionally, nonmagnetic wide-bandgap metal oxide semiconductors lack these µeV electronic transitions and applications. Here, we demonstrate that these metal oxides can be fabricated as good microwave absorbers using a 2D electron gas plasma resonance at the disorder/order interface generated by a hydrogenation process. Using ZnO and TiO2 nanoparticles as examples, we show that large absorption with reflection loss values as large as -49.0 dB (99.99999%) is obtained in the microwave region. The frequency of absorption can be tuned with the particle size and hydrogenation condition. These results may pave the way for new applications for wide bandgap semiconductors, especially in the µeV regime.

Direct and real-time quantification of tenofovir release from ph-sensitive microparticles into simulated biological fluids using (1)h nuclear magnetic resonance.

In vitro drug release evaluation is a very important step toward the quality control of nano- or micro-particular drug delivery systems. However, most quantitative techniques such as high-performance liquid chromatography requires a dialysis membrane to separate the released free drug from these delivery systems, thus are not capable of direct detection and real-time quantification of the drug release kinetics. This study describes, for the first time, a rapid, specific, and direct method for the real-time quantification of in vitro tenofovir (TNF) release from pH-sensitive microparticles using a Varian 400 MHz (1)H nuclear magnetic resonance ((1)H-NMR) spectrometer. Various analytical performance parameters such as linearity, precision, accuracy, limit of quantification, limit of detection, and robustness were validated according to International Conference on Harmonization (ICH) guidelines. The in vitro release of TNF from microparticles in both simulated vaginal fluid (VFS) and the mixture of VFS and simulated semen fluid was monitored and quantified in real time using (1)H-NMR. The capability of real-time quantification of in vitro drug release from microparticles not only provides a more accurate prediction of its biological behavior in vivo, but is also independent of potential interference from the dialysis membrane.

Hyaluronidase-sensitive nanoparticle templates for triggered release of HIV/AIDS microbicide in vitro.

This study was designed to test the hypothesis that a triggered release of a topical microbicide (tenofovir) from hyaluronic acid nanoparticles (HA-NPs) can be achieved under the influence of hyaluronidase (HAase) enzyme. A fractional factorial experimental design was used to examine the factors [molar concentrations of adipic acid dihydrazide (X1) and 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (X2), volume of acetone (X3) and reaction time (X4)] influencing the responses, Y1; particle mean diameter: PMD (nanometers: nm), Y2; polydispersity index: PDI and Y3; zeta (ζ) potential: (millivolts). The amide bond formation between HA and ADH after cross-linking was confirmed by FT-IR and (13)C-NMR analyses. These NPs were also characterized for cytotoxicity on a human vaginal epithelial cell line and L. crispatus. When formulated with factors X1; 2.49 mM, X2; 9.96 mM, X3; 60 mL, X4; 6 h, HA-NPs exhibited a spherical shape with PMD, PDI, ζ potential, encapsulation efficiency, and drug loading of 70.6 ± 4.1 nm, 0.07 ± 0.02, -38.2 ± 2.8 mV, 51.8 ± 2.4% w/w and 26.1 ± 1.2% w/w, respectively, (n = 3). Unlike for HA based gel, HAase significantly triggered the drug release and HA degradation from the NPs after 24 h (~90% w/w and 65% w/w, respectively); whereas, in its absence, these values were ~39% w/w and 26% w/w, respectively. The NPs were non-cytotoxic to human vaginal VK2/E6E7, End1/E6E7 cells and Lactobacillus crispatus. These data highlight the potential of HAase-sensitive HA-NPs templates for the controlled and vaginal delivery of anti-HIV/AIDS microbicides.

Hydrogenated TiO(2) nanocrystals: a novel microwave absorbing material.

Here, we report, for the first time, hydrogenated TiO2 nanocrystals as a novel and exciting microwave absorbing material, based on an innovative collective-movement-of-interfacial-dipole mechanism which causes collective-interfacial-polarization-amplified microwave absorption at the crystalline/disordered and anatase/rutile interfaces. This mechanism is intriguing and upon further exploration may trigger other new concepts and applications.

Properties of disorder-engineered black titanium dioxide nanoparticles through hydrogenation.

The recent discovery of "black" TiO2 nanoparticles with visible and infrared absorption has triggered an explosion of interest in the application of TiO2 in a diverse set of solar energy systems; however, what a black TiO2 nanoparticle really is remains a mystery. Here we elucidate more properties and try to understand the inner workings of black TiO2 nanoparticles with hydrogenated disorders in a surface layer surrounding a crystalline core. Contrary to traditional findings, Ti(3+) here is not responsible for the visible and infrared absorption of black TiO2, while there is evidence of mid-gap states above the valence band maximum due to the hydrogenated, engineered disorders. The hydrogen atoms, on the other hand, can undergo fast diffusion and exchange. The enhanced hydrogen mobility may be explained by the presence of the hydrogenated, disordered surface layer. This unique structure thus may give TiO2, one of the most-studied oxide materials, a renewed potential.

Spray drying tenofovir loaded mucoadhesive and pH-sensitive microspheres intended for HIV prevention.

PURPOSE: To develop spray dried mucoadhesive and pH-sensitive microspheres (MS) based on polymethacrylate salt intended for vaginal delivery of tenofovir (a model HIV microbicide) and assess their critical biological responses. METHODS: The formulation variables and process parameters are screened and optimized using a 2(4-1) fractional factorial design. The MS are characterized for size, zeta potential, yield, encapsulation efficiency, Carr's index, drug loading, in vitro release, cytotoxicity, inflammatory responses and mucoadhesion. RESULTS: The optimal MS formulation has an average size of 4.73µm, zeta potential of -26.3mV, 68.9% yield, encapsulation efficiency of 88.7%, Carr's index of 28.3 and drug loading of 2% (w/w). The MS formulation release 91.7% of its payload in the presence of simulated human semen. At a concentration of 1mg/ml, the MS are noncytotoxic to vaginal endocervical/epithelial cells and Lactobacillus crispatus when compared to control media. There is also no statistically significant level of inflammatory cytokine (IL1-α, IL-1ß, IL-6, IL-8, and IP-10) release triggered by these MS. Their percent mucoadhesion is 2-fold higher than that of 1% HEC gel formulation. CONCLUSION: These data suggest the promise of using such MS as an alternative controlled microbicide delivery template by intravaginal route for HIV prevention.

The local physical structure of amorphous hydrogenated boron carbide: insights from magic angle spinning solid-state NMR spectroscopy.

Magic angle spinning solid-state nuclear magnetic resonance spectroscopy techniques are applied to the elucidation of the local physical structure of an intermediate product in the plasma-enhanced chemical vapour deposition of thin-film amorphous hydrogenated boron carbide (B(x)C:H(y)) from an orthocarborane precursor. Experimental chemical shifts are compared with theoretical shift predictions from ab initio calculations of model molecular compounds to assign atomic chemical environments, while Lee-Goldburg cross-polarization and heteronuclear recoupling experiments are used to confirm atomic connectivities. A model for the B(x)C:H(y) intermediate is proposed wherein the solid is dominated by predominantly hydrogenated carborane icosahedra that are lightly cross-linked via nonhydrogenated intraicosahedral B atoms, either directly through B-B bonds or through extraicosahedral hydrocarbon chains. While there is no clear evidence for extraicosahedral B aside from boron oxides, ∼40% of the C is found to exist as extraicosahedral hydrocarbon species that are intimately bound within the icosahedral network rather than in segregated phases.

Solid state 2H NMR analysis of furanose ring dynamics in DNA containing uracil.

DNA damage has been implicated in numerous human diseases, particularly cancer, and the aging process. Single-base lesions, such as uracil, in DNA can be cytotoxic or mutagenic and are recognized by a DNA glycosylase during the process of base excision repair. Increased dynamic properties in lesion-containing DNAs have been suggested to assist recognition and specificity. Deuterium solid-state nuclear magnetic resonance (SSNMR) has been used to directly observe local dynamics of the furanose ring within a uracil:adenine (U:A) base pair and compared to a normal thymine:adenine (T:A) base pair. Quadrupole echo lineshapes, , and relaxation data were collected, and computer modeling was performed. The results indicate that the relaxation times are identical within the experimental error, the solid lineshapes are essentially indistinguishable above the noise level, and our lineshapes are best fit with a model that does not have significant local motions. Therefore, U:A base pair furanose rings appear to have essentially identical dynamic properties as a normal T:A base pair, and the local dynamics of the furanose ring are unlikely to be the sole arbiter for uracil recognition and specificity in U:A base pairs.

Spectroscopic analysis of interactions between alkylated silanes and alumina nanoporous membranes.

Transport across alumina nanoporous membranes can be altered via surface attachment of alkylated trimethoxysilane compounds. The mechanism of attachment has been previously assumed to be monolayer silane coverage through full chemisorption regardless of reaction conditions. This chemisorption arises via covalent Si-O-Al bond formation resulting from condensation between the three putative silanols (due to hydrolysis of the three Si-OCH(3) bonds) and hydroxides present on the alumina surface. If this model was correct, methanol would be produced in large quantities in the reaction solution, and the methoxy moieties would no longer be present on the silane molecule. The results presented in this paper utilized FT-IR and both solution and solid-state NMR to examine the chemical nature of octadecyltrimethoxysilane (ODTMS) present on the alumina surface. The FT-IR results confirm the presence of the silane on the membrane. The (1)H solution NMR results indicate small but detectable methanol production during attachment. The solid-state NMR results demonstrate that the methoxy proton NMR integrated peak intensities remain in nearly the same ratios present in the free silane, concluding that the majority of methoxy groups are intact while the silane is attached to the membrane surface. These three results suggest that monolayer surface coverage and chemisorption through full covalent bonding is not the primary means of attachment for ODTMS on the surface of alumina nanomembranes under these reaction conditions.

Conformational constraints in solid-state NMR of uniformly labeled polypeptides from double single-quantum-filtered rotational echo double resonance.

A solid-state nuclear magnetic resonance (NMR) technique is described for obtaining constraints on the backbone conformation of a protein or peptide that is prepared with uniform (15)N,(13)C labeling of consecutive pairs of amino acids or of longer segments. The technique, called double single-quantum-filtered rotational echo double resonance (DSQ-REDOR), uses frequency-selective REDOR to prepare DSQ coherences involving directly bonded backbone (13)CO and (15)NH sites, to dephase these coherences under longer-range (15)NH-(13)CO dipole-dipole couplings in a conformationally dependent manner, and to convert the remaining DSQ coherences to detectable transverse (13)C-spin polarization. The efficacy of DSQ-REDOR is demonstrated in experiments on two isotopically labeled samples, the helical peptide MB(i + 4)EK and the amyloid-forming peptide Abeta(11-25).

Parallel beta-sheets and polar zippers in amyloid fibrils formed by residues 10-39 of the yeast prion protein Ure2p.

We report the results of solid-state nuclear magnetic resonance (NMR) and atomic force microscopy measurements on amyloid fibrils formed by residues 10-39 of the yeast prion protein Ure2p (Ure2p(10)(-)(39)). Measurements of intermolecular (13)C-(13)C nuclear magnetic dipole-dipole couplings indicate that Ure2p(10)(-)(39) fibrils contain in-register parallel beta-sheets. Measurements of intermolecular (15)N-(13)C dipole-dipole couplings, using a new solid-state NMR technique called DSQ-REDOR, are consistent with hydrogen bonds between side chain amide groups of Gln18 residues. Such side chain hydrogen bonding interactions have been called "polar zippers" by M. F. Perutz and have been proposed to stabilize amyloid fibrils formed by peptides with glutamine- and asparagine-rich sequences, such as Ure2p(10)(-)(39). We propose that polar zipper interactions account for the in-register parallel beta-sheet structure in Ure2p(10)(-)(39) fibrils and that similar peptides will also exhibit parallel beta-sheet structures in amyloid fibrils. We present molecular models for Ure2p(10)(-)(39) fibrils that are consistent with available experimental data. Finally, we show that solid-state (13)C NMR chemical shifts for (13)C-labeled Ure2p(10)(-)(39) fibrils are insensitive to hydration level, indicating that the fibril structure is not affected by the presence or absence of bulk water.