Single-chain glycopolymer folding via host-guest interactions and its unprecedented effect on DC-SIGN binding

Reversible self-folding actions of natural biomacromolecules play crucial roles for specific and unique biological functions in Nature. Hence, controlled folding of single polymer chains has attracted significant attention in recent years. Herein, reversible single-chain folded glycopolymer structures in α-shape with different density of sugar moieties in the knot were created. The influence of folding as well as the sugar density in the knot was investigated on the binding capability with lectins, such as ConA, DC-SIGN and DC-SIGNR. The synthesis of triblock glycocopolymers bearing β-CD and adamantane for the host-guest interaction and also mannose residues for the lectin interaction was achieved using the reversible addition-fragmentation chain transfer (RAFT) polymerization technique. The reversible single-chain folding of glycopolymers was achieved under a high dilution of an aqueous solution and the self-assembled folding was monitored by 2D nuclear overhauser enhancement spectroscopy (NOESY) NMR and dynamic light scattering. The lectin binding profiles consistently provided an unprecedented effect of single chain folding as the single-chain folded structures enhanced greatly the binding ability in comparison to the unfolded linear structures

Mannosylated poly(ethylene imine) copolymers enhance saRNA uptake and expression in human skin explants

Messenger RNA (mRNA) is a promising platform for both vaccines and therapeutics, and self-amplifying RNA (saRNA) is particularly advantageous, as it enables higher protein expression and dose minimization. Here, we present a delivery platform for targeted delivery of saRNA using mannosylated poly(ethylene imine) (PEI) enabled by the host–guest interaction between cyclodextrin and adamantane. We show that the host–guest complexation does not interfere with the electrostatic interaction with saRNA and observed that increasing the degree of mannosylation inhibited transfection efficiency in vitro, but enhanced the number of cells expressing GFP by 8-fold in human skin explants. Besides, increasing the ratio of glycopolymer to saRNA also enhanced the percentage of transfected cells ex vivo. We identified that these mannosylated PEIs specifically increased protein expression in the epithelial cells resident in human skin in a mannose-dependent manner. This platform is promising for further study of glycosylation of PEI and targeted saRNA delivery

Nitrosocarbonyl Hetero-Diels–Alder Cycloaddition: A New Tool for Conjugation

It is demonstrated that nitrosocarbonyl hetero-Diels-Alder chemistry is an efficient and versatile reaction that can be applied in macromolecular synthesis. Polyethylene glycol functionalized with a hydroxamic acid moiety undergoes facile coupling with cyclopentadiene-terminated polystyrene, through a copper-catalyzed as well as thermal hetero-Diels-Alder reaction. The mild and orthogonal methods used to carry out this reaction make it an attractive method for the synthesis of block copolymers. The resulting block copolymers were analyzed and characterized using GPC and NMR. The product materials could be subjected to thermal retro [4 + 2] cycloaddition, allowing for the liberation of the individual polymer chains and subsequent recycling of the diene-terminated polymers. © 2014 American Chemical Society

Synthesis of carboxylated derivatives of poly(isobutylene-co-isoprene) by azide–alkyne “click” chemistry

The final publication is available at Springer via https://dx.doi.org/10.1038/s41428-018-0130-yThe synthesis of carboxylated derivatives of poly(isobutylene-co-isoprene) (isobutylene–isoprene rubber, IIR) with substitution levels ranging from 1 to 4 mol% and different spacer lengths was accomplished through azide–alkyne Huisgen cycloaddition. Azido-functionalized IIR was first prepared by reacting brominated IIR with sodium azide to full conversion in a 90:10 tetrahydrofuran/N,N-dimethylacetamide mixture. The click reaction of azido-functionalized IIR with acetylenic acids, which was carried out using the copper(I) bromide/N,N,N′,N″,N″-pentamethyldiethylenetriamine catalyst system in tetrahydrofuran, yielded carboxylated IIRs. The products were characterized by 1H NMR and FT-IR spectroscopy, and their molecular weight was determined by size exclusion chromatography analysis. The conversion to carboxylated groups reached up to 100% as determined by NMR spectroscopy but was highly dependent on the type of solvent and the amounts of catalysts and reactants used in the procedures.ARLANXEO Canada Inc.Natural Sciences and Engineering Research Council (NSERC) of Canad

Lower critical solution temperature behavior of comb and graft shaped poly[oligo(2-ethyl-2-oxazoline)methacrylate]s

Comb and graft polymers with lower critical solution temperature (LCST) behavior based on hydrophilic oligo(2-ethyl-2-oxazoline) side chains and a hydrophobic methacrylate backbone were synthesized using the macromonomer method. Well-defined oligo(2-ethyl-2-oxazoline) methacrylate (OEtOxMA) macromono- mers were obtained by direct end-capping of living oligo(2-ethyl-2-oxazoline) chains with in situ formed triethylammonium methacrylate. The macromonomers were subsequently polymerized in a controlled manner using the reversible addition-fragmentation chain transfer (RAFT) polymerization technique yielding a series of comb polymers with varying side chain length and backbone length. In addition, a series of graft copolymers were prepared by copolymerizing OEtOxMA with methyl methacrylate (MMA, 40-80 mol %). The copolymers were characterized by 1H NMR spectroscopy, size exclusion chromatography (SEC), and, partially, by matrix- assisted laser desorption ionization (MALDI-TOF) mass spectrometry. The LCST behavior of aqueous polymer solutions was investigated by turbidity measurements revealing cloud points that can be tuned from 35 to 80 °C by variation of the MMA content. © 2009 American Chemical Society

Pessimism Reduction in Crosstalk Noise Aware STA

Abstract — High performance circuits are facing increasingly severe signal integrity problems due to crosstalk noise and crosstalk noise awareness has become an integral part of static timing analysis (STA). Existing crosstalk noise aware STA methods compute noise induced delay uncertainty on a net by net basis and in a pessimistic way, without considering the overlap bounds of the victim and aggressor timing windows and realistic delay impact on early and late signal arrival times. Since crosstalk induced delay on indivudial nets contribute cumulatively on data and clock paths, even small amounts of pessimism in computation can add up to produce several unrealistic timing violations. Unlike glitch noise analysis where noise often attenuates during propagation, quality of delay noise analysis is severely affected by any pessimism in noise estimation and can unnecessarily cost valuable silicon and design resources for fixing unreal violations. In this paper, we propose two temporal techniques to reduce pessimism in crosstalk noise aware STA. The first method, “effective delay noise”, is a net based method where the exact overlap points of victim and aggressor timing windows are considered to obtain the part of delay noise that actually impacts early and late signal arrival times. The second method, “path based delay noise”, is a path based method where the reduced arrival uncertainty of the nets of a given path are utilized for pessimism reduction. We also propose a novel “uncertainty propagation ” technique as part of the second method, which results in an iteration free crosstalk noise aware STA of the path with significantly reduced pessimism. The two techniques are combined in a proposed methodology that is compatible with existing industrial static timing analyzers with very little computational overhead compared to the traditional noise aware STA and a significant improvement in eliminating unreal violations. The proposed techniques resulted in 77% reduction of worst case negative slack and 57 % reduction in the number of failing paths in the setup analysis of a 90nm industrial design. I