Recent developments in isocyanide based multicomponent reactions in applied chemistry

Universal sample preparation method for proteome analysis

Proper regulation and management of energy, substrate diversity and quantity, as well as macromolecular synthesis and breakdown processes, are fundamental to cellular and organismal survival and are paramount to health. Cellular and multicellular organization are defended by the immune response, a robust and critical system through which self is distinguished from non-self, pathogenic signals are recognized and eliminated, and tissue homeostasis is safeguarded. Many layers of evolutionarily conserved interactions occur between immune response and metabolism. Proper maintenance of this delicate balance is crucial for health and has important implications for many pathological states such as obesity, diabetes, and other chronic non-communicable diseases.

Inflammation, metaflammation and immunometabolic disorders

The intestine represents the largest compartment of the immune system. It is continually exposed to antigens and immunomodulatory agents from the diet and the commensal microbiota, and it is the port of entry for many clinically important pathogens. Intestinal immune processes are also increasingly implicated in controlling disease development elsewhere in the body. In this Review, we detail the anatomical and physiological distinctions that are observed in the small and large intestines, and we suggest how these may account for the diversity in the immune apparatus that is seen throughout the intestine. We describe how the distribution of innate, adaptive and innate-like immune cells varies in different segments of the intestine and discuss the environmental factors that may influence this. Finally, we consider the implications of regional immune specialization for inflammatory disease in the intestine.

Regional specialization within the intestinal immune system

Vaccines containing novel adjuvant formulations are increasingly reaching advanced development and licensing stages, providing new tools to fill previously unmet clinical needs. However, many adjuvants fail during product development owing to factors such as manufacturability, stability, lack of effectiveness, unacceptable levels of tolerability or safety concerns. This Review outlines the potential benefits of adjuvants in current and future vaccines and describes the importance of formulation and mechanisms of action of adjuvants. Moreover, we emphasize safety considerations and other crucial aspects in the clinical development of effective adjuvants that will help facilitate effective next-generation vaccines against devastating infectious diseases.

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Key roles of adjuvants in modern vaccines

An Improved Synthetic Route to the Potent Angiogenesis Inhibitor

A15 The heparan sulfate (HS) mimetic PI-88 is a mixture of highly sulfated oligosaccharides about to commence Phase III clinical evaluation for post-resection hepatocellular carcinoma. Its anticancer properties are attributed to the inhibition of both angiogenesis and heparanase activity. Analogs of PI-88 have been designed with enhanced chemical and biological properties. The advances in the chemistry of these compounds have been achieved without adversely influencing the inhibition of heparanase activity or the binding to proangiogenic growth factors such as FGF-2 or VEGF. Heparan sulfate mimetic compounds have been rationally designed and characterized using biological assays such as endothelial cell proliferation, tube formation, the rat aortic assay for angiogenesis and the B16 melanoma model. Several of these compounds exhibit potent antiproliferative, antiangiogenic and anticancer properties in comparison to PI-88. For example, the IC 50 values of these novel HS mimetics in growth factor-induced HUVEC proliferation assays are up to 30-fold (for FGF-2) or 60-fold (for VEGF) lower compared to PI-88. Potent inhibition is also observed in the tube formation or rat aortic angiogenesis assay while anticoagulant activity, which has been responsible for injection site bruising, has been largely obviated. A number of compounds also exhibit potent antitumor activity in the B16 melanoma model. The current data support the design and development of heparan sulfate mimetics as potent antiangiogenic compounds and anticancer agents.

Heparan sulfate mimetics - potent angiogenesis inhibitors for cancer therapy

Exogenous Sorbitol Improves Maize Tolerance to Drought Through Up-Regulating Antioxidant System and Endogenous Sorbitol Biosynthesis

A focused library of novel, sulfated glycoconjugates was synthesized by utilizing carbohydrate-derived blocks in the four-component Ugi condensation. Library members comprise a sulfated monosaccharide linked by various spacers to either an aromatic or monosulfated moiety, or a second sulfated monosaccharide. The affinities of these heparan sulfate (HS) mimetics for the HS-binding fibroblast growth factors FGF-1 and FGF-2 were measured via a surface plasmon resonance solution affinity assay.

Application of the Four-Component Ugi Condensation for the Preparation of Sulfated Glycoconjugate Libraries.

La presente invention concerne de nouveaux composes de Formule (1), des compositions pharmaceutiques incluant de tels composes et des methodes d'emploi de tels composes en tant qu'outils de recherche biologique ou en tant qu'agents ou medicaments dans la modulation du Recepteur 2 active par les proteases (PAR2) et dans le traitement d'un sujet risquant de contracter ou sensible a une maladie ou un trouble, ou souffrant d'une maladie ou d'un trouble associe a une activite indesirable de PAR2.

Ligong Liu

Papers

An Improved Synthetic Route to the Potent Angiogenesis Inhibitor

Heparan sulfate mimetics - potent angiogenesis inhibitors for cancer therapy

Exogenous Sorbitol Improves Maize Tolerance to Drought Through Up-Regulating Antioxidant System and Endogenous Sorbitol Biosynthesis

Application of the Four-Component Ugi Condensation for the Preparation of Sulfated Glycoconjugate Libraries.

Modulateurs des récepteurs activés par les protéases