Design, Synthesis and Pro-Inflammatory Activity of Palmitoylated Derivatives of Thioglycolic Acid as New Immunomodulators.

The immune system is essential for the defense against infections and is critically implicated in various disorders, including immunodeficiency, autoimmunity, inflammation and cancer. The current study includes a new design of palmitoylated derivatives of thioglycolic acids (PTGAs) capable of triggering innate immune responses. The new series were accessible through a three-step synthetic route, including N-palmitoylation, Claisen-Schmidt condensation and thia-Michael addition.

Anti-Allergic and Anti-Inflammatory Effects of Lidocaine-Derived Organic Compounds in a House Dust Mite-Induced Allergic Rhinitis Mouse Model.

Allergic rhinitis (AR) is a common chronic disease that significantly impacts the quality of life. Lidocaine is known to have anti-inflammatory and immunomodulatory effects. This study evaluated the effect of lidocaine analogs in a (DP)-induced AR mouse model.

Effects of Lidocaine-Derived Organic Compounds on Eosinophil Activation and Survival.

Lidocaine, a local anesthetic, is known to possess anti-inflammatory properties. However, its clinical use is limited by inconveniences, such as its local synesthetic effects. This study evaluated lidocaine analogs designed and synthesized to overcome the disadvantages of lidocaine, having anti-inflammatory properties.

Chemical composition and anticholinesterase activity of (Roxb.) Leenh. essential oil.

Essential oils obtained from medicinal plants show high therapeutic potential against several types of pathologies, including Alzheimer's disease. The purpose of this work was to study the chemical composition and anticholinesterase inhibitory activity of the essential oil obtained from leaves collected from Malaysia. Twenty-four components were identified using gas chromatography-flame ionization detection (GC-FID) and gas chromatography/mass spectrometry (GC-MS), which represent 99.

Ketorolac-fluconazole: A New Combination Reverting Resistance in from Acute Myeloid Leukemia Patients on Induction Chemotherapy: In vitro Study.

Background And Objectives: is a significant source of morbidity and mortality for patients with acute myeloid leukemia (AML). Prolonged use of fluconazole as empirical antifungal prophylaxis in AML patients leads to overexpression of efflux pump genes that resulted in the emergence of azole-resistant species. Consequently, the introduction of a new strategy to improve the management of infections is an urgent need.

Auxiliary-assisted chemical ubiquitylation of NEMO and linear extension by HOIP.

The ubiquitylation of NF-κB essential modulator (NEMO) is part of the intracellular immune signalling pathway. Monoubiquitylated NEMO is required for exploring the mechanism of NEMO linear ubiquitylation by LUBAC (linear ubiquitin chain assembly complex), but is not accessible by biological techniques. Here we perform the chemical ubiquitylation of NEMO using a ligation auxiliary, which only requires a two-step synthesis, and is easily installed onto the lysine side-chain.

Synthesis of Amide Backbone-Modified Peptides.

Solubility is a key property of peptides and of central importance to the success of solid-phase peptide synthesis and subsequent peptide purification and handling. Substitution of the backbone amide bond can dramatically increase peptide solubility. Backbone amide bond protection works by preventing the formation of interchain association and can be used both to synthesize aggregation-prone peptide sequences on solid phase and to improve solubility of a peptide post synthesis.

A backbone amide protecting group for overcoming difficult sequences and suppressing aspartimide formation.

A backbone amide bond protecting group, 2-hydroxy-4-methoxy-5-nitrobenzyl (Hmnb), improved the synthesis of aggregation and aspartimide-prone peptides. Introduction of Hmnb is automated and carried out during peptide assembly by addition of 4-methoxy-5-nitrosalicylaldehyde to the peptidyl-resin and on-resin reduction to the secondary amine. Acylation of the hindered secondary amine is aided by the formation of an internal nitrophenol ester that undergoes a favourable O,N intramolecular acyl transfer.

Automated synthesis of backbone protected peptides.

The synthesis of peptides rich in aggregation prone sequences can be improved with backbone protection. We report the automated introduction of backbone protection to a peptide. This new method was applied in a fully-automated synthesis, giving improved handling, quality and yield of several challenging target sequences.

Immune and anticancer responses elicited by fully synthetic aberrantly glycosylated MUC1 tripartite vaccines modified by a TLR2 or TLR9 agonist.

The mucin MUC1 is overexpressed and aberrantly glycosylated by many epithelial cancer cells manifested by truncated O-linked saccharides. Although tumor-associated MUC1 has generated considerable attention because of its potential for the development of a therapeutic cancer vaccine, it has been difficult to design constructs that consistently induce cytotoxic T-lymphocytes (CTLs) and ADCC-mediating antibodies specific for the tumor form of MUC1. We have designed, chemically synthesized, and immunologically examined vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous Thelper peptide, and a TLR2 (Pam3 CysSK4 ) or TLR9 (CpG-ODN 1826) agonist.

Design of fully synthetic, self-adjuvanting vaccine incorporating the tumor-associated carbohydrate Tn antigen and lipoamino acid-based Toll-like receptor 2 ligand.

Overexpression of certain tumor-associated carbohydrate antigens (TACA) caused by malignant transformation offers promising targets to develop novel antitumor vaccines, provided the ability to break their inherent low immunogenicity and overcome the tolerance of the immune system. We designed, synthesized, and immunologically evaluated a number of fully synthetic new chimeric constructs incorporating a cluster of the most common TACA (known as Tn antigen) covalently attached to T-cell peptide epitopes derived from polio virus and ovalbumin and included a synthetic built-in adjuvant consisting of two 16-carbon lipoamino acids. Vaccine candidates were able to induce significantly strong antibody responses in mice without the need for any additional adjuvant, carrier protein, or special pharmaceutical preparation (e.

Immunological evaluation of lipopeptide group A streptococcus (GAS) vaccine: structure-activity relationship.

Streptococcus pyogenes (group A streptococcus, GAS) is a Gram-positive bacterial pathogen responsible for a wide variety of diseases. To date, GAS vaccine development has focused primarily on the M-protein. The M-protein is highly variable at the amino (N)-terminus (determining serotype) but is conserved at the carboxyl (C)-terminus.

Simple synthetic toll-like receptor 2 ligands.

Stimulation of toll-like receptor 2 (TLR2) by bacterial lipoproteins induces fast non-specific immune responses against pathogens followed by slow but specific adaptive immune responses. Development of synthetic TLR2 agonists/antagonists would be useful in the prevention of different infectious and immunologic disorders. The current study reports synthesis and TLR2 activity of two simple TLR2 ligands, which feature minimal structural requirement for TLR2 activity (two long lipid chains) and stimulate agonistic activity at nanomolar concentration.

Synthesis and immunological evaluation of self-adjuvanting glycolipopeptide vaccine candidates.

Synthesis of four glycolipids with different number of lauroyl groups on glucose or cellobiose as scaffolds is described. Their immunological evaluations either admixed with or covalently linked to J8, a peptide antigen derived from the C-terminus of the antiphagocytic M-protein of group A streptococcus, are also investigated. Administration of mixtures of J8 and glycolipids to B10BR (H-2(k)) mice induced low-levels of J8-specific IgG antibodies.