Toward predicting silver ion binding in proteins.

The binding of metal ions in proteins is often crucial for their function and hence for life. Silver is known to possess antimicrobial properties, yet little is known about the exact molecular mechanism of action. Based on the silver binding tetrapeptide moieties HXXM, and MXXH found in the silver efflux pump protein SilE, we studied the influence of the individual amino acids X and X and found trends that may be important in general metal ion binding in proteins.

Deconstructing Best-in-Class Neoglycoclusters as a Tool for Dissecting Key Multivalent Processes in Glycosidase Inhibition.

Multivalency represents an appealing option to modulate selectivity in enzyme inhibition and transform moderate glycosidase inhibitors into highly potent ones. The rational design of multivalent inhibitors is however challenging because global affinity enhancement relies on several interconnected local mechanistic events, whose relative impact is unknown. So far, the largest multivalent effects ever reported for a non-polymeric glycosidase inhibitor have been obtained with cyclopeptoid-based inhibitors of Jack bean α-mannosidase (JBα-man).

Titration of Apparent In-Cellula Affinities of Protein-Protein Interactions.

A genetic assay permits simultaneous quantification of two interacting proteins and their bound fraction at the single-cell level using flow cytometry. Apparent in-cellula affinities of protein-protein interactions can be extracted from the acquired data through a titration-like analysis. The applicability of this approach is demonstrated on a diverse set of interactions with proteins from different families and organisms and with in-vitro dissociation constants ranging from picomolar to micromolar.

Structure-activity relationship and molecular modelling studies of quinazolinedione derivatives MMV665916 as potential antimalarial agent.

A series of new quinazolinedione derivatives have been readily synthesized and evaluated for their in vitro antiplasmodial growth inhibition activity. Most of the compounds inhibited P. falciparum FcB1 strain in the low to medium micromolar concentration.