Sweet Drugs for Bad Bugs: A Glycomimetic Strategy against the DC-SIGN-Mediated Dissemination of SARS-CoV-2.

The C-type lectin receptor DC-SIGN is a pattern recognition receptor expressed on macrophages and dendritic cells. It has been identified as a promiscuous entry receptor for many pathogens, including epidemic and pandemic viruses such as SARS-CoV-2, Ebola virus, and HIV-1. In the context of the recent SARS-CoV-2 pandemic, DC-SIGN-mediated virus dissemination and stimulation of innate immune responses has been implicated as a potential factor in the development of severe COVID-19.

Ligand Pathways in Nuclear Receptors.

Nuclear receptors (NRs) are ligand-inducible transcription factors that play an essential role in a multitude of physiological processes as well as diseases, rendering them attractive drug targets. Crystal structures revealed the binding site of NRs to be buried in the core of the protein, with no obvious route for ligands to access this cavity. The process of ligand binding is known to be an often-neglected contributor to the efficacy of drug candidates and is thought to influence the selectivity and specificity of NRs.

The price of flexibility - a case study on septanoses as pyranose mimetics.

Seven-membered ring mimetics of mannose were studied as ligands for the mannose-specific bacterial lectin FimH, which plays an essential role in the first step of urinary tract infections (UTI). A competitive binding assay and isothermal titration calorimetry (ITC) experiments indicated an approximately ten-fold lower affinity for the seven-membered ring mannose mimetic 2--heptyl-1,6-anhydro-d--d-galactitol () compared to -heptyl α-d-mannopyranoside (), resulting exclusively from a loss of conformational entropy. Investigations by solution NMR, X-ray crystallography, and molecular modeling revealed that establishes a superimposable H-bond network compared to mannoside , but at the price of a high entropic penalty due to the loss of its pronounced conformational flexibility.

Conformational switch of the bacterial adhesin FimH in the absence of the regulatory domain: Engineering a minimalistic allosteric system.

For many biological processes such as ligand binding, enzymatic catalysis, or protein folding, allosteric regulation of protein conformation and dynamics is fundamentally important. One example is the bacterial adhesin FimH, where the C-terminal pilin domain exerts negative allosteric control over binding of the N-terminal lectin domain to mannosylated ligands on host cells. When the lectin and pilin domains are separated under shear stress, the FimH-ligand interaction switches in a so-called catch-bond mechanism from the low- to high-affinity state.

Oligohis-tags: mechanisms of binding to Ni2+-NTA surfaces.

Since immobilized metal ion affinity chromatography (IMAC) was first reported, several modifications have been developed. Among them, Ni(2+) immobilized by chelation with nitrilotriacetic acid (NTA) bound to a solid support has become the most common method for the purification of proteins carrying either a C- or N-terminal histidine (His) tag. Despite its broad application in protein purification, only little is known about the binding properties of the His-tag, and therefore almost no thermodynamic and kinetic data are available.

Synthesis of aryl sialosides using Mitsunobu conditions.

Mitsunobu conditions for the efficient synthesis of aryl alpha/beta-sialosides were developed. An oxidative work-up procedure was employed to avoid a cumbersome chromatographic separation from the 2,3-dehydro derivative of sialic acid, which is formed as a side-product.

New trends in the production of pharmaceutical granules: batch versus continuous processing.

In the pharmaceutical industry, the production of granules is based on a batch concept. This concept offers many advantages with respect to quality assurance as a batch can be accepted or rejected. However, the scale-up of the batch size may lead to problems.

New trends in the production of pharmaceutical granules: the classical batch concept and the problem of scale-up.

The moist agglomeration process, i.e. the wet massing, screening, and subsequent drying is often a critical unit operation.