A5056474822- Protein purification and stability
- Monoclonal and Polyclonal Antibodies Research
- Viral Infectious Diseases and Gene Expression in Insects
- Transgenic Plants and Applications
- Protein Structure and Dynamics
- SARS-CoV-2 and COVID-19 Research
- Glycosylation and Glycoproteins Research
- Biosimilars and Bioanalytical Methods
- Viral Infections and Immunology Research
- Influenza Virus Research Studies
- thermodynamics and calorimetric analyses
- Animal Virus Infections Studies
- Amyloidosis: Diagnosis, Treatment, Outcomes
- COVID-19 Clinical Research Studies
- Complement system in diseases
- Chronic Lymphocytic Leukemia Research
- Analytical Chemistry and Chromatography
- Digestive system and related health
- Enzyme Structure and Function
- Protein Kinase Regulation and GTPase Signaling
- Viral gastroenteritis research and epidemiology
- Galectins and Cancer Biology
- Microfluidic and Bio-sensing Technologies
- Proteins in Food Systems
- Bacteriophages and microbial interactions
Technical University of Munich
2020-2025
Ghent University
2022-2025
Ludwig-Maximilians-Universität München
2018-2023
Center for Integrated Protein Science Munich
2021-2022
Antibody drugs should exhibit not only high-binding affinity for their target antigens but also favorable physicochemical drug-like properties. Such biophysical properties are essential the successful development of antibody drug products. The traditional approaches used in require significant experimentation to produce, optimize, and characterize many candidates. Therefore, it is attractive integrate new methods that can optimize process selecting antibodies with both desired target-binding...
Various stability indicating techniques find application in the early stage development of novel therapeutic protein candidates. Some these are used to select formulation conditions that provide high physical stability. Such approach is highly dependent on reliability technique used. In this work, we present a case study which evaluate ability differential scanning fluorimetry (DSF) and isothermal chemical denaturation (ICD) predict model monoclonal antibody during accelerated studies....
Intrinsic differential scanning fluorimetry (DSF) is essential for analyzing protein thermal stability. Until now, intrinsic DSF was characterized by medium throughput and high consumable costs. Here, we present a microplate-based approach that enables the measurement of up to 384 samples in parallel consuming only 10 μL per sample. We systematically test benchmark new against gold-standard methods such as microcalorimetry circular dichroism. Using range model proteins sample conditions,...
Therapeutic protein candidates should exhibit favorable properties that render them suitable to become drugs. Nevertheless, there are no well-established guidelines for the efficient selection of proteinaceous molecules with desired features during early stage development. Such can emerge only from a large body published research employs orthogonal techniques characterize therapeutic proteins in different formulations. In this work, we share study on diverse group proteins, including their...
Determining the temperature at which thermal unfolding of a protein starts becoming irreversible is relevant for many areas research. Until now, published methods cannot determine, within reasonable time frame and with moderate sample consumption, exposure that causing unfolding. We present modulated scanning fluorimetry (MSF) share software (MSF Analyzer), can be used to derive nonreversibility curves from series incremental cycles performed on only 10 μL samples, consuming as low few...
Abstract Antibodies bind antigens via flexible loops called complementarity-determining regions (CDRs). These are usually 6-20 residues long. However, some bovine antibodies have ultra-long CDRs comprising more than 50 organized in a stalk and disulfide-rich knob. The design features of this structural unit its influence on antibody stability remained enigmatic. Here, we show that the length is critical for folding with an CDR disulfide bonds knob do not contribute to stability; they...
Abstract Coronavirus infections are a world-wide threat to human health. A promising strategy develop broadly active antiviral is the use of fusion proteins consisting an antibody IgG Fc region and ACE2 domain which viral spike bind. Here we create based on IgM scaffolds. The hexameric ACE2-IgM-Fc fusions can be efficiently produced in mammalian cells they neutralize infectious virus with picomolar affinity thus surpassing monomeric by up 96-fold potency. In addition, ACE2-IgM shows...
SARS-CoV-2 enters host cells after binding through its spike glycoprotein to the angiotensin-converting enzyme 2 (ACE2) receptor. Soluble ACE2 ectodomains bind and neutralize virus, yet their short in vivo half-live limits therapeutic use. This limitation can be overcome by fusing fragment crystallizable (Fc) part of human immunoglobulin G (IgG) ectodomain, but this bears risk Fc-receptor activation antibody-dependent cellular cytotoxicity. Here, we describe optimized ACE2-IgG4-Fc fusion...
The efficient development of new therapeutic antibodies relies on developability assessment with biophysical and computational methods to find molecules drug-like properties such as resistance aggregation. Despite the many novel approaches select well-behaved proteins, antibody aggregation during storage is still challenging predict. For this reason, there a high demand for that can identify aggregation-resistant antibodies. Here, we show three straightforward techniques from dataset 13...
Abstract The angiotensin-converting enzyme 2 (ACE2) is a viral receptor used by sarbecoviruses to infect cells. Fusion proteins comprising extracellular ACE2 domains and the Fc part of immunoglobulins exhibit high virus neutralization efficiency, but structure stability these molecules are poorly understood. We show that although hinge between IgG4-Fc highly flexible, conformational dynamics two restricted their association. Interestingly, moiety much lower than part. found chemical...
Abstract The antigen‐binding sites in conventional antibodies are formed by hypervariable complementarity‐determining regions (CDRs) from both heavy chains (HCs) and light (LCs). A deviation this paradigm is found a subset of bovine that bind antigens via an ultra‐long CDR. HCs bearing CDRs pair with restricted set highly conserved LCs convey stability to the antibody. Despite importance these LCs, their specific features remained unknown. Here, we show LC exhibits distinct combination...