Dimeric ligands for GPCRs involved in human reproduction: synthesis and biological evaluation

Dimeric ligands for G-protein coupled receptors that are involved in human reproduction, namely the gonadotropin releasing hormone receptor, the luteinizing hormone receptor and the follicle-stimulating hormone receptor, were synthesized and biologically evaluated.The project has been financially supported by the Council for Chemical Sciences of the Netherlands Organization for Scientific Research (CW-NWO) and the Schering-Plough Research Institute (Oss).UBL - phd migration 201

Metabolic labeling probes for interrogation of the host-pathogen interaction

Bacterial infections are still one of the leading causes of death worldwide; despite the near-ubiquitous availability of antibiotics. With antibiotic resistance on the rise, there is an urgent need for novel classes of antibiotic drugs. One particularly troublesome class of bacteria are those that have evolved highly efficacious mechanisms for surviving inside the host. These contribute to their virulence by immune evasion, and make them harder to treat with antibiotics due to their residence inside intracellular membrane-limited compartments. This has sparked the development of new chemical reporter molecules and bioorthogonal probes that can be metabolically incorporated into bacteria to provide insights into their activity status. In this review, we provide an overview of several classes of metabolic labeling probes capable of targeting either the peptidoglycan cell wall, the mycomembrane of mycobacteria and corynebacteria, or specific bacterial proteins. In addition, we highlight several important insights that have been made using these metabolic labeling probes.Microbial Biotechnolog

Multifunctional, Multivalent PIC Polymer Scaffolds for Targeting Antigen-Specific, Autoreactive B Cells

Multivalent scaffolds that carry multiple molecules with immunophenotyping or immunomodulatory properties areinvaluable tools for studying and modulating specific functions ofhuman immune responses. So far, streptavidin-biotin-basedtetramers have been widely used for B-cell immunophenotypingpurposes. However, the utility of these tetramers is limited by theirtetravalency, the inherent immunogenicity of streptavidin (abacterial protein that can potentially be recognized by B cells),and the limited feasibility to functionalize these reagents. This has rendered tetramers suboptimal for studying rare, in particular,antigen-specific B-cell populations in the context of clinical applications. Here, we used polyisocyanopeptides (PICs), multivalentpolymeric scaffolds functionalized with around 50 peptide antigens, to detect autoreactive B cells in the peripheral blood of patientswith rheumatoid arthritis. To explore the potential immunomodulatory functionalities, we functionalized PICs with autoantigenicpeptides and a trisaccharide CD22 ligand to inhibit autoreactive B-cell activation through interference with the B-cell receptoractivation pathway, as evidenced by reduced phospho-Syk expression upon PIC binding. Given the possibilities to functionalizePICs, our data demonstrate that the modular and versatile character of PIC scaffolds makes them promising candidates for futureclinical applications in B-cell-mediated diseasesPathophysiology and treatment of rheumatic disease

Chemical Control over T-Cell Activation in Vivo Using Deprotection of trans-Cyclooctene-Modified Epitopes

Tumorimmunolog

Vinylboronic Acids as Fast Reacting, Synthetically Accessible, and Stable Bioorthogonal Reactants in the Carboni-Lindsey Reaction

Contains fulltext : 163349.pdf (publisher's version ) (Open Access

Using light to shape chemical gradients for parallel and automated analysis of chemotaxis

Contains fulltext : 144898.pdf (publisher's version ) (Open Access

Phenylglyoxal-Based Visualization of Citrullinated Proteins on Western Blots

Contains fulltext : 144977.pdf (publisher's version ) (Open Access

Phenylglyoxal-based visualization of citrullinated proteins on Western blots

Contains fulltext : 152578.pdf (publisher's version ) (Open Access)Citrullination is the conversion of peptidylarginine to peptidylcitrulline, which is catalyzed by peptidylarginine deiminases. This conversion is involved in different physiological processes and is associated with several diseases, including cancer and rheumatoid arthritis. A common method to detect citrullinated proteins relies on anti-modified citrulline antibodies directed to a specific chemical modification of the citrulline side chain. Here, we describe a versatile, antibody-independent method for the detection of citrullinated proteins on a membrane, based on the selective reaction of phenylglyoxal with the ureido group of citrulline under highly acidic conditions. The method makes use of 4-azidophenylglyoxal, which, after reaction with citrullinated proteins, can be visualized with alkyne-conjugated probes. The sensitivity of this procedure, using an alkyne-biotin probe, appeared to be comparable to the antibody-based detection method and independent of the sequence surrounding the citrulline

Highly Stable and Selective Tetrazines for the Coordination-Assisted Bioorthogonal Ligation with Vinylboronic Acids

Contains fulltext : 196225.pdf (publisher's version ) (Open Access

Making forest carbon markets work for low-income producers

Forest carbon projects could potentially enhance the incomes and environment of hundreds of thousands, if not millions, of some of the world's poorest people, while providing real, climate-significant carbon offsets. But this opportunity will only be realized by adopting suitable rules for the CDM, applying innovations by business and social entrepreneurs to lower transaction costs, and taking public action to reduce risks to both investors and communities. This infobrief provides key points for making forest carbon markets work for low-income producers, and recommendations for the Clean Development Mechanism