Sweet Janus Particles: Multifunctional Inhibitors of Carbohydrate-Based Bacterial Adhesion.

Escherichia coli and other bacteria use adhesion receptors, such as FimH, to attach to carbohydrates on the cell surface as the first step of colonization and infection. Efficient inhibitors that block these interactions for infection treatment are multivalent carbohydrate-functionalized scaffolds. However, these multivalent systems often lead to the formation of large clusters of bacteria, which may pose problems for clearing bacteria from the infected site. Here, we present Man-containing Janus particles (JPs) decorated on one side with glycomacromolecules to target Man-specific adhesion receptors of E. coli. On the other side, poly(N-isopropylacrylamide) is attached to the particle hemisphere, providing temperature-dependent sterical shielding against binding and cluster formation. While homogeneously functionalized particles cluster with multiple bacteria to form large aggregates, glycofunctionalized JPs are able to form aggregates only with individual bacteria. The formation of large aggregates from the JP-decorated single bacteria can still be induced in a second step by increasing the temperature and making use of the collapse of the PNIPAM hemisphere. This is the first time that carbohydrate-functionalized JPs have been derived and used as inhibitors of bacterial adhesion. Furthermore, the developed JPs offer well-controlled single bacterial inhibition in combination with cluster formation upon an external stimulus, which is not achievable with conventional carbohydrate-functionalized particles.

Lewis Base-Brønsted Acid-Enzyme Catalysis in Enantioselective Multistep One-Pot Syntheses.

Establishing one-pot, multi-step protocols combining different types of catalysts is one important goal for increasing efficiency in modern organic synthesis. In particular, the high potential of biocatalysts still needs to be harvested. Based on an in-depth mechanistic investigation of a new organocatalytic protocol employing two catalysts {1,4-diazabicyclo[2.2.2]octane (DABCO); benzoic acid (BzOH)}, a sequence was established providing starting materials for enzymatic refinement (ene reductase; alcohol dehydrogenase): A gram-scale access to a variety of enantiopure key building blocks for natural product syntheses was enabled utilizing up to six catalytic steps within the same reaction vessel.

Autonomy in consumer choice.

We propose that autonomy is a crucial aspect of consumer choice. We offer a definition that situates autonomy among related constructs in philosophy and psychology, contrast actual with perceived autonomy in consumer contexts, examine the resilience of perceived autonomy, and sketch out an agenda for research into the role of perceived autonomy in an evolving marketplace increasingly characterized by automation.

Prophylactic Antiviral Activity of Sulfated Glycomimetic Oligomers and Polymers.

In this work, we investigate the potential of highly sulfated synthetic glycomimetics to act as inhibitors of viral binding/infection. Our results indicate that both long-chain glycopolymers and short-chain glycooligomers are capable of preventing viral infection. Notably, glycopolymers efficiently inhibit Human Papillomavirus (HPV16) infection in vitro and maintain their antiviral activity in vivo, while the glycooligomers exert their inhibitory function post attachment of viruses to cells. Moreover, when we tested the potential for broader activity against several other human pathogenic viruses, we observed broad-spectrum antiviral activity of these compounds beyond our initial assumptions. While the compounds tested displayed a range of antiviral efficacies, viruses with rather diverse glycan specificities such as Herpes Simplex Virus (HSV), Influenza A Virus (IAV), and Merkel Cell Polyomavirus (MCPyV) could be targeted. This opens new opportunities to develop broadly active glycomimetic inhibitors of viral entry and infection.

Split-and-Combine Approach Towards Branched Precision Glycomacromolecules and Their Lectin Binding Behavior.

Previously, monodisperse and sequence-controlled oligo(amidoamine) scaffolds were synthesized based on the step-wise assembly of tailor-made building blocks on a solid support that allow for the multivalent presentation of sugar ligands. Here, we extend on this concept using a split-and-combine approach to gain access to a small library of linear and branched glycomacromolecules. Azide side chains were introduced in the scaffold by the use of a novel building block allowing for copper-mediated azide-alkyne cycloaddition (CuAAC) of readily available propargyl-functionalized glycans. In the first stage, after assembly of the linear scaffold on solid support, the batch was divided into two. One part of the resin-bound oligomers was end-capped and further used as backbone and the other part was functionalized with propargylated α-d-mannopyranoside in the sidechain, end capped with an alkyne functionality and finally cleaved from solid support to give the branching arm. In the second stage, the linear, glycosylated and alkynylated arms were then coupled to the end capped backbone via CuAAC. In this way, branched glycomacromolecules with two and three branches, respectively, have been synthesized carrying from two to six sugar residues per molecule. Both, linear arms and branched glycomacromolecules were then subjected to a lectin binding assay using surface plasmon resonance (SPR) and model lectin Concanavalin A (Con A) showing the effect of branching as well as valency on the binding kinetics.