Synthesis of star-branched poly(vinyl alcohol) and ice recrystallization inhibition activity

Antifreeze proteins are potent inhibitors of ice crystal growth (recrystallization), which is a highly desirable property for cryopreservation and other low temperature applications. It has emerged that relatively simple polymers based on poly(vinyl alcohol) can mimic this activity, but the link between architecture and activity is not known. Here, a trifunctional xanthate was designed and synthesized to prepare star-branched poly(vinyl alcohols) by RAFT/Xanthate mediated polymerization, and their ice growth inhibition activity probed for the first time. The trifunctional agent design affords the formation of well-defined star polymers, with no evidence of star-star linking, even at high conversions, and narrow molecular weight dispersity. It is observed that three-arm stars have identical activity to two-armed (i.e. linear) equivalents, suggesting that the total hydrodynamic size of the polymer (diameter three-arm ~ two-arm) rather than total valence of the functional groups is the key descriptor of activit

Ethanol induces the formation of water-permeable defects in model bilayers of skin lipids

We show that ethanol can induce the formation of water-permeable defects in model membranes of skin, providing a fresh perspective on ethanol as a membrane modulator. We rationalise our findings in terms of the chemical nature of ethanol, i.e., a combination of its hydrogen bonding propensity and amphiphilic character

Complete structure of an epithelial keratin dimer: implications for intermediate filament assembly

Keratins are cytoskeletal proteins that hierarchically arrange into filaments, starting with the dimer sub-unit. They are integral to the structural support of cells, in skin, hair and nails. In skin, keratin is thought to play a critical role in conferring the barrier properties and elasticity of skin. In general, the keratin dimer is broadly described by a tri-domain structure: a head, a central rod and a tail. As yet, no atomistic-scale picture of the entire dimer structure exists; this information is pivotal for establishing molecular-level connections between structure and function in intermediate filament proteins. The roles of the head and tail domains in facilitating keratin filament assembly and function remain as open questions. To address these, we report results of molecular dynamics simulations of the entire epithelial human K1/K10 keratin dimer. Our findings comprise: (1) the first three-dimensional structural models of the complete dimer unit, comprising of the head, rod and tail domains; (2) new insights into the chirality of the rod-domain twist gained from analysis of the full domain structure; (3) evidence for tri-subdomain partitioning in the head and tail domains; and, (4) identification of the residue characteristics that mediate non-covalent contact between the chains in the dimer. Our findings are immediately applicable to other epithelial keratins, such as K8/K18 and K5/K14, and to intermediate filament proteins in general

Synthesis of hydroxylated group IV metal oxides inside hollow graphitised carbon nanofibers: nano-sponges and nanoreactors for enhanced decontamination of organophosphates

The confinement and enhanced catalytic properties of hydroxylated group IV metal oxide nanostructures inside hollow graphitised carbon nanofibers (GNF) has been demonstrated. GNF – a structural analogue of carbon nanotubes – were effectively filled with suitable precursor molecules of metal chlorides from the gas and liquid phases. Subsequent basecatalysed hydrolysis afforded amorphous, nanostructured hydroxylated metal oxide (MOx(OH)y where M = Zr, Ti, and Hf) thin films, which coat the internal surfaces of GNF. This versatile and general strategy allows the chemical composition and morphology of the encapsulated material to be modified by varying the conditions used for hydrolysis and post-synthesis thermal treatment. The increased Lewis acidic properties and high surface area of the zirconium composite promote the catalysed hydrolysis of dimethyl nitrophenyl phosphate (DMNP) – a toxic organophosphorus chemical. A four-fold enhancement in the rate of DMNP hydrolysis relative to its separate constituent components was observed, highlighting the surprising synergistic abilities of this composite material to perform both as a ‘nano-sponge’, absorbing the harmful compounds inside the GNF, and a nanoreactor, enhancing the local concentration of organophosphate around the hydroxylated metal oxide species, leading to improved catalytic performance

Building Energy Use and Conservation in Cycle VIII of the Texas Institutional Conservation Program

Sixty-two technical assistance (energy audit) reports by twelve different consulting firms representing fifteen independent school districts, nine hospitals, and five colleges have been reviewed to assess energy use characteristics and recommended energy saving measures. Such measures include both maintenance and operation (H&O) measures (generally regarded as "low-cost, no-cost") and energy conservation (ECH) measures (generally more expensive and requiring outside skills). Implementation cost, annual savings of energy and costs, and paybacks were reported for all M&Os and ECHs. Measures were broken down by the consulting firms according to energy use characteristics and categories, and it was determined that average costs for electricity and gas, before implementation of M&Os and ECHs, were $0.0596/KWH and$4.85/MMBTU respectively. The total implementation cost and projected annual savings for the M&Os are $73,000 and$223,000 respectively, yielding a four-month payback. The corresponding results for implementation of ECHs are $2,232,000 and$555,000, resulting in a four-year payback. Also, some obvious problems in the preparation of technical assistance reports along with the general background and implementation of the Institutional Conservation Program in Texas, resulting from the National Energy Act of 1978, are discussed

An Analysis of Efficiency Improvements in Residential Sized Heat Pumps

The objectives of this study included: (1) development of classes of heat pumps, (2) evaluation and selection of a suitable heat pump design model, (3) characterization of suitable baseline heat pump designs, (4) selection of design options that can be used to improve heat pump efficiency, and (5) development of heat pump designs to cover the whole spectrum of efficiencies available today and those that may be technologically feasible in the next few years

Pathogenesis of Scleroderma

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65784/1/j.1365-4362.1984.tb05678.x.pd

Macrocyclisation of small peptides enabled by oxetane incorporation

Cyclic peptides are an important source of new drugs but are challenging to produce synthetically. We show that head-to-tail peptide macrocyclisations are greatly improved, as measured by isolated yields, reaction rates and product distribution, by substitution of one of the backbone amide C═O bonds with an oxetane ring. The cyclisation precursors are easily made by standard solution- or solid-phase peptide synthesis techniques. Macrocyclisations across a range of challenging ring sizes (tetra-, penta- and hexapeptides) are enabled by incorporation of this turn-inducing element. Oxetane incorporation is shown to be superior to other established amino acid modifications such as N-methylation. The positional dependence of the modification on cyclisation efficiency is mapped using a cyclic peptide of sequence LAGAY. We provide the first direct experimental evidence that oxetane modification induces a turn in linear peptide backbones, through the observation of dNN (i, i + 2) and dαN (i, i + 2) NOEs, which offers an explanation for these improvements. For cyclic peptide, cLAGAY, a combination of NMR derived distance restraints and molecular dynamics simulations are used to show that this modification alters the backbone conformation in proximity to the oxetane, with the flexibility of the ring reduced and a new intramolecular H-bond established. Finally, we incorporated an oxetane into a cyclic pentapeptide inhibitor of Aminopeptidase N, a transmembrane metalloprotease overexpressed on the surface of cancer cells. The inhibitor, cCNGRC, displayed similar IC50 values in the presence or absence of an oxetane at the glycine residue, indicating that bioactivity is fully retained upon amide C═O bond replacement

Synthesis and Functionalization of Azetidine-Containing Small Macrocyclic Peptides

Cyclic peptides are increasingly important structures in drugs but their development can be impeded by difficulties associated with their synthesis. Here, we introduce the 3-aminoazetidine (3-AAz) subunit as a new turn-inducing element for the efficient synthesis of small head-to-tail cyclic peptides. Greatly improved cyclizations of tetra-, penta- and hexapeptides (28 examples) under standard reaction conditions are achieved by introduction of this element within the linear peptide precursor. Post-cyclization deprotection of the amino acid side chains with strong acid is realized without degradation of the strained four-membered azetidine. A special feature of this chemistry is that further late-stage modification of the resultant macrocyclic peptides can be achieved via the 3-AAz unit. This is done by: (i) chemoselective deprotection and substitution at the azetidine nitrogen, or by (ii) a click-based approach employing a 2-propynyl carbamate on the azetidine nitrogen. In this way, a range of dye and biotin tagged macrocycles are readily produced. Structural insights gained by XRD analysis of a cyclic tetrapeptide indicate that the azetidine ring encourages access to the less stable, all-trans conformation. Moreover, introduction of a 3-AAz into a representative cyclohexapeptide improves stability towards proteases compared to the homodetic macrocycle