Absztrakt Background Peripheral blood oxygen monitoring via chemoreceptors in the carotid body (CB) is an integral function of the autonomic cardiorespiratory regulation. The presence of the purinergic P2Y12 receptor (P2Y12R) has been implicated in CB; however, the exact role of…
Abstract The most fundamental topological units of proteins are their autonomously folded domains. The rapid and reliable chemical synthesis of domains in the range of 5–10 kDa in size, remains a challenge. Their bacterial expression is cumbersome, especially when chemical…
Abstract The synthesis of D-glucosamine-1-carboxylic acid based β-sugar amino acids (β-SAAs) is typically performed in nine consecutive steps via an inefficient OAc → Br → CN conversion protocol with low overall yield. Here, we present the improved and more efficient synthesis of both Fmoc-GlcAPC-OH and…
Abstract Myostatin, an important negative regulator of muscle mass, is a therapeutic target for muscle atrophic disorders such as muscular dystrophy. Thus, the inhibition of myostatin presents a strategy to treat these disorders. It has long been established that the…
Abstract In this work, catalytically significant states of the oncogenic G12C variant of KRAS, those of Mg2+-free and Mg2+-bound GDP-loaded forms, have been determined using CS-Rosetta software and NMR-data-driven molecular dynamics simulations. There are several Mg2+-bound G12C KRAS/GDP structures deposited…
Abstract The cis-trans isomerization of amide bonds leads to wide range of structural and functional changes in proteins and can easily be the rate-limiting step in folding. The trans isomer is thermodynamically more stable than the cis, nevertheless the cis form can play a role in biopolymers’…
Abstract The structure of porcine AAP (pAAP) in a covalently bound complex with meropenem was determined by cryo-EM to 2.1 Å resolution, showing the mammalian serine-protease inhibited by a carbapenem antibiotic. AAP is a modulator of the ubiquitin-proteasome degradation system…
Absztrakt Background: Haemostasis is a crucial process by which the body stops bleeding. It is achieved by the formation of a platelet plug, which is strengthened by formation of a fibrin mesh mediated by the coagulation cascade. In proinflammatory and prothrombotic…
In the Pharmaceutical Development Technology pillar, we develop highly efficient, environmentally sound processes for the production of active ingredients and the pharmaceutical products they can be made into. Our work includes the realisation of new catalytic hydrogenations, chemo-, regioselective and…
The main objectives of the Neuropharmacology Pillar are to conduct research on inflammatory and degenerative mechanisms in the nervous system, synthesis and development of new molecules, exploitation of new indications for existing drugs, development of screening tests in translational models,…