TY  - JOUR
A1  - Sinn, Stefan
A1  - Eichler, Mirjam
A1  - Müller, Lothar
A1  - Bünger, Daniel
A1  - Groll, Jüergen
A1  - Ziemer, Gerhard
A1  - Rupp, Frank
A1  - Northoff, Hinnak
A1  - Geis-Gerstorfer, Jürgen
A1  - Gehring, Frank K.
A1  - Wendel, Hans P.
T1  - NCO-sP(EO-stat-PO) Coatings on Gold Sensors-a QCM Study of Hemocompatibility
JF  - Sensors
N2  - The reliability of implantable blood sensors is often hampered by unspecific adsorption of plasma proteins and blood cells. This not only leads to a loss of sensor signal over time, but can also result in undesired host vs. graft reactions. Within this study we evaluated the hemocompatibility of isocyanate conjugated star shaped polytheylene oxide-polypropylene oxide co-polymers NCO-sP(EO-stat-PO) when applied to gold surfaces as an auspicious coating material for gold sputtered blood contacting sensors. Quartz crystal microbalance (QCM) sensors were coated with ultrathin NCO-sP(EO-stat-PO) films and compared with uncoated gold sensors. Protein resistance was assessed by QCM measurements with fibrinogen solution and platelet poor plasma (PPP), followed by quantification of fibrinogen adsorption. Hemocompatibility was tested by incubation with human platelet rich plasma (PRP). Thrombin antithrombin-III complex (TAT), beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) were used as coagulation activation markers. Furthermore, scanning electron microscopy (SEM) was used to visualize platelet adhesion to the sensor surfaces. Compared to uncoated gold sensors, NCO-sP(EO-stat-PO) coated sensors revealed significant better resistance against protein adsorption, lower TAT generation and a lower amount of adherent platelets. Moreover, coating with ultrathin NCO-sP(EO-stat-PO) films creates a cell resistant hemocompatible surface on gold that increases the chance of prolonged sensor functionality and can easily be modified with specific receptor molecules.
KW  - self-assembled monolayers
KW  - 316L stainless-steel
KW  - protein adsorption
KW  - poly(ethylene glycol)
KW  - platelet-adhesion
KW  - blood-plasma
KW  - surfaces
KW  - biosensor
KW  - cell self-assembled monolayers
KW  - cell coagulation
KW  - surface coating
KW  - biosensors
KW  - hemocompatibility
KW  - QCM
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-141110
VL  - 11
IS  - 5
ER  - 
TY  - JOUR
A1  - Bothe, Sebastian
A1  - Hänzelmann, Petra
A1  - Böhler, Stephan
A1  - Kehrein, Josef
A1  - Zehe, Markus
A1  - Wiedemann, Christoph
A1  - Hellmich, Ute A.
A1  - Brenk, Ruth
A1  - Schindelin, Hermann
A1  - Sotriffer, Christoph
T1  - Fragment screening using biolayer interferometry reveals ligands targeting the SHP-motif binding site of the AAA+ ATPase p97
JF  - Communications Chemistry
N2  - Biosensor techniques have become increasingly important for fragment-based drug discovery during the last years. The AAA+ ATPase p97 is an essential protein with key roles in protein homeostasis and a possible target for cancer chemotherapy. Currently available p97 inhibitors address its ATPase activity and globally impair p97-mediated processes. In contrast, inhibition of cofactor binding to the N-domain by a protein-protein-interaction inhibitor would enable the selective targeting of specific p97 functions. Here, we describe a biolayer interferometry-based fragment screen targeting the N-domain of p97 and demonstrate that a region known as SHP-motif binding site can be targeted with small molecules. Guided by molecular dynamics simulations, the binding sites of selected screening hits were postulated and experimentally validated using protein- and ligand-based NMR techniques, as well as X-ray crystallography, ultimately resulting in the first structure of a small molecule in complex with the N-domain of p97. The identified fragments provide insights into how this region could be targeted and present first chemical starting points for the development of a protein-protein interaction inhibitor preventing the binding of selected cofactors to p97.
KW  - fragment screening
KW  - AAA+ ATPase p97
KW  - biosensor
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300821
VL  - 5
IS  - 1
ER  -