Perfluoroaryl Bicyclic Cell‐Penetrating Peptides for Delivery of Antisense Oligonucleotides

Exon‐skipping antisense oligonucleotides are effective treatments for genetic diseases, yet exon‐skipping activity requires that these macromolecules reach the nucleus. While cell‐penetrating peptides can improve delivery, proteolytic instability often limits efficacy. It is hypothesized that the bicyclization of arginine‐rich peptides would improve their stability and their ability to deliver oligonucleotides into the nucleus. Two methods were introduced for the synthesis of arginine‐rich bicyclic peptides using cysteine perfluoroarylation chemistry. Then, the bicyclic peptides were covalently linked to a phosphorodiamidate morpholino oligonucleotide (PMO) and assayed for exon skipping activity. The perfluoroaryl cyclic and bicyclic peptides improved PMO activity roughly 14‐fold over the unconjugated PMO. The bicyclic peptides exhibited increased proteolytic stability relative to the monocycle, demonstrating that perfluoroaryl bicyclic peptides are potent and stable delivery agents.     

Combined Short-Term Glucose Starvation and Chemotherapy in 3D Colorectal Cancer Cell Culture Decreases 14-3-3 Family Protein Expression and Phenotypic Response to Therapy

Short-term glucose starvation prior to chemotherapy has the potential to preferentially weaken cancer cells, making them more likely to succumb to treatment, while protecting normal cells. In this study, we used 3D cell cultures of colorectal cancer and assessed the effects of short-term glucose starvation and chemotherapy compared to treatment of either individually. We evaluated both phenotypic changes and protein expression levels. Our findings indicate that the combined treatment results in more significant phenotypic responses, including decreased cell viability and clonogenicity. These phenotypic responses can be explained by the decreased expression of LDHA and 14-3-3 family proteins, which were found only in the combined treatment groups. This study indicates that short-term glucose starvation has the potential to increase the efficacy of current cancer treatment regimes.

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An eco-friendly tandem tosylation/Ferrier N-glycosylation of amines catalyzed by Er(OTf)3 in 2-MeTHF

Er(OTf)₃ in 2-MeTHF provides a new and eco-friendly process for Ferrier glycosylation of sulfonamides and amino acids with various N-nucleophiles.The stereoselective synthesis of 2,3-unsaturated-N-pseudoglycals was carried out with 3,4,6-tri-O-acetyl-d-glucal and different nucleophiles affording good results in a short time.     

Associating divisors with quadratic differentials on Klein surfaces

We extend the notion and basic properties of quadratic differential divisors to a Klein surface, using the corresponding form’s divisors from the double cover of the Klein surface.     

Concentration on minimal submanifolds for a Yamabe-type problem

We construct solutions to a Yamabe-type problem on a Riemannian manifold M without boundary and of dimension greater than 2, with nonlinearity close to higher critical Sobolev exponents. These solutions concentrate their mass around a nondegenerate minimal submanifold of M, provided a certain geometric condition involving the sectional curvatures is satisfied. A connection with the solution of a class of PDE's on the submanifold with a singular term of attractive or repulsive type is established.     

Blow‐up phenomena in chemotaxis systems with a source term

This paper deals with a parabolic–parabolic Keller–Segel‐type system in a bounded domain of , {N = 2;3}, under different boundary conditions, with time‐dependent coefficients and a positive source term. The solutions may blow up in finite time t^?; and under appropriate assumptions on data, explicit lower bounds for blow‐up time are obtained when blow up occurs. Copyright © 2015 John Wiley & Sons, Ltd.