Supramolecular chirality : from molecules to helical assemblies in polar media

+148hlm.;24c

Supramolecular polymer

A polymer comprising monomeric units linked via 4 H-bridges and bound within said polymer via a different bond. The bond via the H-bridges is much stronger than with known supramolecular polymers

Van molecuul tot cel

No abstract

Lower extremity vascular disease

Purpose: We performed a systematic review to assess (1) to what extent Incident Reporting Systems (IRS) on the adult ICU meet the criteria of the WHO Draft Guidelines for Adverse Event Reporting and Learning Systems, (2) to what extent the IRSs comply with the four aspects of the iterative quality loop and (3) whether IRSs have led to improvement measures in clinical practice. Data sources: The authors searched multiple electronic databases from 1966 until June 26th 2014. Study Selection: Studies were included if they reported incident reporting systems on the adult ICU. Data Extraction: Data on study design, characteristics of the incident reporting system, implementation, feedback and improvement measures were collected using structured data extraction forms. Results of data synthesis: A total of 2098 studies were identified and 36 studies reported IRSs on the adult ICU. Studies were divided into: ICU specific IRSs and general IRSs. Items of the WHO checklist were assessed and categorized into the four phases of the iterative quality loop. Conclusion: None of the IRSs completely fulfilled the WHO checklist criteria. With respect to the iterative loop, data input and data collection are well established but not much attention was given to analyzing incidents and to give feedback. This resulted in an administrative report system, rather than the much desired instrument for change of practice and increase of quality as an IRS can only effectively contribute to improve patient safety and quality of care if more attention is given to analyzing incidents and feedback.Perioperative Medicine: Efficacy, Safety and Outcom

Communication in critical care : measuring and monitoring quality of care to improve patient safety

Healthcare systems have become more effective but are also more complex with greater use of new technologies and interventions. This can result in incidents and life threatening events during patients’ hospitalization and affect the quality of care and patient safety. The objective of the investigations was to assess the tools that are available to measure and monitor quality of care in critically ill patients and the effect of implementing some of these tools on quality of care.LUMC / Geneeskund

Hydrophobicity Directed Chiral Self-Assembly and Aggregation-Induced Emission:Diacetylene-Cored Pseudopeptide Chiral Dopants

Here we delineate simple and tunable hydrophobically driven chiral functional assemblies of diacetylene cored pseudopeptides. These amino acid appended, rigid core dialkynes constitute promising chiral supramolecular building blocks for materials properties engineering. The chiral appended amino acid elements allow for simple tuning of solubility and interaction properties as well as governing chirality, while the central dialkyne core can impart hydrophobically driven assembly and Aggregation Induced Emission (AIE) properties. The self-assembly of these rod-like dialkynes can be regulated by tuning the solvent environment, with for example self-assembly into vesicles in acetonitrile and into helical organization with AIE in a H 2 O/DMSO mixture. Of additional high interest, these supramolecular materials, themselves devoid of liquid crystal (LC) properties, can induce chirality into non-chiral LC matrices with high helical twisting power. </p

A Thermodynamic Model for Multivalency in 14-3-3 Protein-Protein Interactions

Protein-protein interactions (PPIs) are at the core of molecular control over cellular function. Multivalency in PPI formation, such as via proteins with multiple binding sites and different valencies, requires fundamental understanding to address correlated challenges in pathologies and drug development. Thermodynamic binding models are needed to provide frameworks for describing multivalent PPIs. We established a model based on ditopic host-guest systems featuring the effective molarity, a hallmark property of multivalency, as a prime parameter governing the intramolecular binding in divalent interactions. By way of illustration, we study the interaction of the bivalent 14-3-3 protein scaffold with both the nonavalent CFTR and the hexavalent LRRK2 proteins, determining the underlying thermodynamics and providing insights into the role of individual sites in the context of the multivalent platform. Fitting of binding data reveals enthalpy-entropy correlation in both systems. Simulations of speciations for the entire phosphorylated protein domains reveal that the CFTR protein preferably binds to 14-3-3 by combinations including the strongest binding site pS768, but that other binding sites take over when this site is eliminated, leading to only a minor decrease in total affinity for 14-3-3. For LRRK2, two binding sites dominate the complex formation with 14-3-3, but the distantly located pS1444 site also plays a role in complex formation. Thermodynamic modeling of these multivalent PPIs allowed analyzing and predicting the effects of individual sites regarding their modulation via, for example, (de)phosphorylation or small-molecule targeting. The results specifically bring forward the potential of PPI stabilization, as an entry for drug discovery for multivalent PPIs.</p

Carborane–β-cyclodextrin complexes as a supramolecular connector for bioactive surfaces

Supramolecular chemistry provides an attractive entry to generate dynamic and well-controlled bioactive surfaces. Novel host–guest systems are urgently needed to provide a broader affinity and applicability portfolio. A synthetic strategy to carborane–peptide bioconjugates was therefore developed to provide an entry to monovalent supramolecular functionalization of β-cyclodextrin coated surfaces. The β-cyclodextrin·carborane–cRGD surfaces are formed efficiently and with high affinity as demonstrated by IR-RAS, WCA, and QCM-D, compare favourable to existing bio-active host–guest surface assemblies, and display an efficient bioactivity, as illustrated by a strong functional effect of the supramolecular system on the cell adhesion and spreading properties. Cells seeded on the supramolecular surface displaying bioactive peptide epitopes exhibited a more elongated morphology, focal adhesions, and stronger cell adhesion compared to control surfaces. This highlights the macroscopic functionality of the novel supramolecular immobilization strategy

Discovery of 14-3-3 PPI Stabilizers by Extension of an Amidine-Substituted Thiophene Fragment

Protein-protein interaction (PPI) modulation is a promising approach in drug discovery with the potential to expand the 'druggable' proteome and develop new therapeutic strategies. While there have been significant advancements in methodologies for developing PPI inhibitors, there is a relative scarcity of literature describing the 'bottom-up' development of PPI stabilizers (Molecular Glues). The hub protein 14-3-3 and its interactome provide an excellent platform for exploring conceptual approaches to PPI modulation, including evolution of chemical matter for Molecular Glues. In this study, we employed a fragment extension strategy to discover stabilizers for the complex of 14-3-3 protein and an Estrogen Receptor alpha-derived peptide (ERα). A focused library of analogues derived from an amidine-substituted thiophene fragment enhanced the affinity of the 14-3-3/ERα complex up to 6.2-fold. Structure-activity relationship (SAR) analysis underscored the importance of the newly added, aromatic side chain with a certain degree of rigidity. X-ray structural analysis revealed a unique intermolecular π-π stacking binding mode of the most active analogues, resulting in the simultaneous binding of two molecules to the PPI binding pocket. Notably, analogue 11 displayed selective stabilization of the 14-3-3/ERα complex.</p