Smaller,Stronger, More Stable: Peptide Variants of a SARS-CoV-2 Neutralizing Miniprotein

Based on the structure of a de novo designed miniprotein (LCB1) in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, we have generated and characterized truncated peptide variants of LCB1, which present only two of the three LCB1 helices, and which fully retained the virus neutralizing potency against different SARS-CoV-2 variants of concern (VOC). This antiviral activity was even 10-fold stronger for a cyclic variant of the two-helix peptides, as compared to the full-length peptide. Furthermore, the proteolytic stability of the cyclic peptide was substantially improved, rendering it a better potential candidate for SARS-CoV-2 therapy. In a more mechanistic approach, the peptides also served as tools to dissect the role of individual mutations in the RBD for the susceptibility of the resulting virus variants to neutralization by the peptides. As the peptides reported here were generated through chemical synthesis, rather than recombinant protein expression, they are amenable to further chemical modification, including the incorporation of a wide range of non-proteinogenic amino acids, with the aim to further stabilize the peptides against proteolytic degradation, as well as to improve the strength, as well the breadth, of their virus neutralizing capacity.     

Kristallin-flüssige Ketoximester

Liquid-crystallin Ketoxime Esters Disubstituted acetophenoneoximebenzoates 1a – q , 2a – j , a – d , 4a – b and 5a – b are nematic liquid crystals that exhibit remarkable thermal stability and, dependent on their terminal groups, relative low melting points. Binary and ternary mixtures, for which also the melting temperatures have been evaluated theoretically, are liquid far below room temperature and stable under the influence of a. c. fields. The substitution of CH₃ by C₂H₅ or n-C₃H₇ in 6a – d and 7 leads to pronounced depressions in the clearing points.     

Intramolekulare Chinhydrone. III. Farbe und Charge-transfer-Wechselwirkungen

Intramolecular Quinhydrones. III. Colour and Charge-transfer Interactions The intensive colour of the crystalline intramolecular quinhydrones 2a – o depends on the substitution and the unsymmetrical bridge-structure. The solutions are yellow coloured. According to the x-ray, i.r.- and u.v./vis-results there are for 2a–o inter, but no intramolecular CT-complexes.     

Tumor Infiltration with CD20+CD73+ B Cells Correlates with Better Outcome in Colorectal Cancer

Immunotherapy has become increasingly important in the treatment of colorectal cancer (CRC). Currently, CD73, also known as ecto-5′-nucleotidase (NT5E), has gained considerable interest as a potential therapeutic target. CD73 is one of the key enzymes catalyzing the conversion of extracellular ATP into adenosine, which in turn exerts potent immune suppressive effects. However, the role of CD73 expression on various cell types within the CRC tumor microenvironment remains unresolved. The expression of CD73 on various cell types has been described recently, but the role of CD73 on B-cells in CRC remains unclear. Therefore, we analyzed CD73 on B-cells, especially on tumor-infiltrating B-cells, in paired tumor and adjacent normal tissue samples from 62 eligible CRC patients. The highest expression of CD73 on tumor-infiltrating B-cells was identified on class-switched memory B-cells, followed by naive B-cells, whereas no CD73 expression was observed on plasmablasts. Clinicopathological correlation analysis revealed that higher CD73⁺ B-cells infiltration in the CRC tumors was associated with better overall survival. Moreover, metastasized patients showed a significantly decreased number of tumor-infiltrating CD73⁺ B-cells. Finally, neoadjuvant therapy correlated with reduced CD73⁺ B-cell numbers and CD73 expression on B-cells in the CRC tumors. As promising new immune therapies are being developed, the role of CD73⁺ B-cells and their subsets in the development of colorectal cancer should be further explored to find new therapeutic options.     

Zum elektrochemischen Verhalten von unsymmetrisch verbrückten Dichinonen

On the Electrochemical Behaviour of Asymmetrically Bridged Diquinones Redox potentials and pK-values of tetravalent asymmetrically bridged diquinones, quinhydrones, and hydroquinones are described and the influences of substituents on these characteristics are discussed.     

Absolute characterization of high numerical aperture microscope objectives utilizing a dipole scatterer

Measuring the aberrations of optical systems is an essential step in the fabrication of high precision optical components. Such a characterization is usually ba...     

Simulating the emergence of norms in different scenarios

This paper deals with EMIL-S, a software tool box which was designed during the EMIL project for the simulation of processes during which norms emerged in an agent society. This tool box implements the cognitive architecture of normative agents which was designed during the EMIL project which is also discussed in other papers in this issue. This implementation is described in necessary detail, and two examples of its application to several different scenarios are given, namely a scenario in which persons involved in micro finance are simulated and learn how to sanction free riders and how to learn from these sanctions, and a scenario in which simulated persons move through a simulated airport where they more often than not have to wait in queues and learn how to behave properly in queues.