Synthetic Multicomponent Nanovaccines Based on the Molecular Co-assembly of β-Peptides Protect against Influenza A Virus.

Peptides with the ability to self-assemble into nanoparticles have emerged as an attractive strategy to design antigen delivery platforms for subunit vaccines. While toll-like receptor (TLR) agonists are promising immunostimulants, their use as soluble agents is limited by their rapid clearance and off-target inflammation. Herein, we harnessed molecular co-assembly to prepare multicomponent cross-β-sheet peptide nanofilaments exposing an antigenic epitope derived from the influenza A virus and a TLR agonist.

Squaramide Tethered Clindamycin, Chloroquine, and Mortiamide Hybrids: Design, Synthesis, and Antimalarial Activity.

Malaria remains one of the major health problems in the world. In this work, a series of squaramide tethered chloroquine, clindamycin, and mortiamide D hybrids have been synthesized to assess their antiplasmodial activity against 3D7 (chloroquine-sensitive) and Dd2 strains of . The most active compound, a simple chloroquine analogue, displayed low nanomolar IC value against both strains (3 nM for 3D7 strain and 18 nM for Dd2 strain).

Protecting-group-free synthesis of clevudine (L-FMAU), a treatment of the hepatitis B virus.

Unnatural nucleoside analogues are valuable research and clinical tools as antiproliferative, antibacterial or antiviral agents. In this context, clevudine (L-FMAU), a reverse transcriptase inhibitor, is currently used for the treatment of the hepatitis B virus. Herein, we describe a new strategy for the preparation of clevudine.

Synthetic development of sugar amino acid oligomers towards novel podophyllotoxin analogues.

In this work, we have developed an approach for the synthesis of sugar amino acid oligomers based on the glucosamine scaffold. We found that the solid-phase approach was unsuccessful for the preparation of sugar amino acid oligomers and the limitation of the liquid-phase approach revolved around the low solubility of larger oligomers. Nevertheless, this strategy allowed the coupling of alkynylated carbohydrate amino acids with podophyllotoxin-bearing an azide functional group yielding novel podophyllotoxin analogues.

A glycan-based plasmonic sensor for prostate cancer diagnosis.

Prostate cancer affects thousands of men who undergo clinical screening tests every year. The main biomarker used for the diagnosis of prostate cancer, prostate specific antigen (PSA), presents limitations that justify investigating new biomarkers to improve reliability. Antibodies against the tumor-associated carbohydrate antigen (Tn), or TACA, develop early in carcinogenesis, making them an interesting alternative as a target for prostate cancer diagnostics.

Polyfluoroglycoside Synthesis via Simple Alkylation of an Anomeric Hydroxyl Group: Access to Fluoroetoposide Analogues.

In this work, we have developed a new approach for the synthesis of fluoroglycoside analogues. This strategy used a simple alkylation protocol and allowed the installation of a simple aglyconic alkane with the β configuration. Moreover, the glycosylation of fluorinated glucoside analogues with 4'-demethylepipodophyllotoxin furnished novel fluoroetoposide analogues.

Synthesis of C-terminal glycopeptides via oxime resin aminolysis.

Natural glycopeptides have been shown to possess interesting biological activities. In this work, we have developed a general solid-phase approach to C-terminal glycopeptides. Taking advantage of oxime resin ester bond nucleophile susceptibility, we optimised the nucleophilic cleavage step with glycosylamines and demonstrated the generality and scope of this method.

Exploring the Chemistry of Non-sticky Sugars: Synthesis of Polyfluorinated Carbohydrate Analogues of d-Allopyranose.

There is a growing interest in the preparation of polyfluorinated carbohydrates. A limited number of fluorohexopyranosides have been used in biological investigations because of the synthetic challenge they present. Hence, we report the synthesis of fluorinated homodimer, fluorodisaccharides, C-terminal fluoroglycopeptides, lipoic acid fluoroglycoconjugate and trifluoroallopyranoside derivatives functionalized at C-6.

Diversity-Oriented Synthesis of Diol-Based Peptidomimetics as Potential HIV Protease Inhibitors and Antitumor Agents.

Peptidomimetic HIV protease inhibitors are an important class of drugs used in the treatment of AIDS. The synthesis of a new type of diol-based peptidomimetics is described. Our route is flexible, uses d-glucal as an inexpensive starting material, and makes minimal use of protection/deprotection cycles.

Randomized, Placebo- and Active-Controlled Crossover Study of the Safety and Efficacy of THVD-102, a Fixed-dose Combination of Oxybutynin and Pilocarpine, in Subjects With Primary Focal Hyperhidrosis.

Background: While muscarinic antagonists (anticholinergics) have shown efficacy in treating primary focal hyperhidrosis (PFH), side effects - most commonly dry mouth - are intolerable for most patients. THVD-102, a fixed-dose combination product has been developed combining oxybutynin, a muscarinic antagonist, and pilocarpine, a muscarinic agonist. The pilocarpine is at a dose level and release profile optimized to correct salivary flow impaired by oxybutynin yet not interfere with the therapeutic muscarinic antagonist effect of oxybutynin upon the sweat glands.

Pulmonary hemodynamic effects of dipyridamole infusion in patients with normal and elevated pulmonary artery systolic pressure receiving PB127.

Background: Intravenous administration of microspheres used as ultrasound contrast agents may potentially alter pulmonary hemodynamics. PB127 (POINT Biomedical Corp., San Carlos, CA) is an investigational ultrasound perfusion-imaging agent used in conjunction with dipyridamole to diagnose coronary artery disease.