TY  - JOUR
A1  - Schmidt, Sebastian
A1  - Zehe, Markus
A1  - Holzgrabe, Ulrike
T1  - Characterization of binding properties of ephedrine derivatives to human alpha-1-acid glycoprotein
JF  - European Journal of Pharmaceutical Sciences
N2  - Most drugs, especially those with acidic or neutral moieties, are bound to the plasma protein albumin, whereas basic drugs are preferentially bound to human alpha-1-acid glycoprotein (AGP). The protein binding of the long-established drugs ephedrine and pseudoephedrine, which are used in the treatment of hypotension and colds, has so far only been studied with albumin. Since in a previous study a stereoselective binding of ephedrine and pseudoephedrine to serum but not to albumin was observed, the aim of this study was to check whether the enantioselective binding behavior of ephedrine and pseudoephedrine, in addition to the derivatives methylephedrine and norephedrine, is due to AGP and to investigate the influence of their different substituents and steric arrangement. Discontinuous ultrafiltration was used for the determination of protein binding. Characterization of ligand-protein interactions of the drugs was obtained by saturation transfer difference nuclear magnetic resonance spectroscopy. Docking experiments were performed to analyze possible ligand-protein interactions. The more basic the ephedrine derivative is, the higher is the affinity to AGP. There was no significant difference in the binding properties between the individual enantiomers and the diastereomers of ephedrine and pseudoephedrine.
KW  - protein binding
KW  - AGP
KW  - ultrafiltration
KW  - saturation transfer difference NMR
KW  - epitope mapping
KW  - ephedrine
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300848
VL  - 181
ER  - 
TY  - JOUR
A1  - Liang, Chunguang
A1  - Bencurova, Elena
A1  - Psota, Eric
A1  - Neurgaonkar, Priya
A1  - Prelog, Martina
A1  - Scheller, Carsten
A1  - Dandekar, Thomas
T1  - Population-predicted MHC class II epitope presentation of SARS-CoV-2 structural proteins correlates to the case fatality rates of COVID-19 in different countries
JF  - International Journal of Molecular Sciences
N2  - We observed substantial differences in predicted Major Histocompatibility Complex II (MHCII) epitope presentation of SARS-CoV-2 proteins for different populations but only minor differences in predicted MHCI epitope presentation. A comparison of this predicted epitope MHC-coverage revealed for the early phase of infection spread (till day 15 after reaching 128 observed infection cases) highly significant negative correlations with the case fatality rate. Specifically, this was observed in different populations for MHC class II presentation of the viral spike protein (p-value: 0.0733 for linear regression), the envelope protein (p-value: 0.023), and the membrane protein (p-value: 0.00053), indicating that the high case fatality rates of COVID-19 observed in some countries seem to be related with poor MHC class II presentation and hence weak adaptive immune response against these viral envelope proteins. Our results highlight the general importance of the SARS-CoV-2 structural proteins in immunological control in early infection spread looking at a global census in various countries and taking case fatality rate into account. Other factors such as health system and control measures become more important after the early spread. Our study should encourage further studies on MHCII alleles as potential risk factors in COVID-19 including assessment of local populations and specific allele distributions.
KW  - COVID-19
KW  - population coverage
KW  - MHC II
KW  - MHC I
KW  - B-cell
KW  - T-cell
KW  - epitope mapping
KW  - lethality rate
KW  - infection spread
KW  - SARS-CoV-2
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258936
SN  - 1422-0067
VL  - 22
IS  - 5
ER  -