Modern drug discovery demands large amounts of high-quality protein and, therefore, begins by expressing target genes in heterologous systems such as bacteria or insect cells. However, some of the most attractive drug targets have proven challenging to clone and express. A technology called Combinatorial Domain Hunting has been developed to express regions or domains of proteins in a non-aggregated form. This technology has been applied to more than 50 targets and, in all cases, high-expressing protein domains have been produced. In many cases, the protein is also non-aggregated, making it ideal for developing assays for screening or determining its X-ray crystal structure.
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http://dx.doi.org/10.1016/j.drudis.2010.03.010 | DOI Listing |
Pept Sci (Hoboken)
November 2024
Department of Pediatrics, Section of Hematology/Oncology, The University of Chicago, Chicago, Illinois 60637, United States of America.
The COVID-19 pandemic drove a uniquely fervent pursuit to explore the potential of peptide, antibody, protein, and small-molecule based antiviral agents against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The interaction between the SARS-CoV2 spike protein with the angiotensin-converting enzyme 2 (ACE2) receptor that mediates viral cell entry was a particularly interesting target given its well described protein-protein interaction (PPI). This PPI is mediated by an α-helical portion of ACE2 binding to the receptor binding domain (RBD) of the spike protein and thought to be susceptible to blockade through molecular mimicry.
View Article and Find Full Text PDFNanoscale Adv
December 2024
Department of Biological Sciences and Engineering, Indian Institute of Technology Palakkad Palakkad Kerala 678 623 India.
Since the initial publication on the first TiCT MXene in 2011, there has been a significant increase in the number of reports on applications of MXenes in various domains. MXenes have emerged as highly promising materials for various biomedical applications, including photothermal therapy (PTT), drug delivery, diagnostic imaging, and biosensing, owing to their fascinating conductivity, mechanical strength, biocompatibility and hydrophilicity. Through surface modification, MXenes can mitigate cytotoxicity, enhance biological stability, and improve histocompatibility, thereby enabling their potential use in biomedical applications.
View Article and Find Full Text PDFCrit Rev Oncog
January 2025
Department of Biotechnology, Dr. B.R. Ambedkar University, Srikakulam 532410, Andhra Pradesh, India.
The heat shock protein 90 kDa (HSP90) is highly conserved across diverse species, including humans, and upregulated in various cancers. As a result, it has been identified as a promising target for advancing anticancer medicine. The introduction of combinatorial chemistry in drug discovery has emphasized the need to develop new technologies in screening, designing, decoding, synthesizing, and screening combinatorial drug libraries.
View Article and Find Full Text PDFBiochemistry
January 2025
Research and Early Development Oncology, Bayer AG, Müllerstr. 178, Berlin 13342, Germany.
The receptor tyrosine kinase EphB4 is involved in tumor angiogenesis, proliferation, and metastasis. Designed ankyrin repeat proteins (DARPins) binding to the EphB4 extracellular domain were identified from a combinatorial library using phage display. Surface plasmon resonance (SPR) allowed us to distinguish between DARPins that either compete with the EphB4 ligand ephrin-B2 for binding to a common site or target a different epitope.
View Article and Find Full Text PDFACS Mater Au
January 2025
Institute for Advanced Materials and Manufacturing, Department of Materials Science and Engineering, Knoxville, Tennessee 37996, United States.
Halide perovskites (HPs) are emerging as key materials in the fight against global warming with well recognized applications, such as photovoltaics, and emergent opportunities, such as photocatalysis for methane removal and environmental remediation. These current and emergent applications are enabled by a unique combination of high absorption coefficients, tunable band gaps, and long carrier diffusion lengths, making them highly efficient for solar energy conversion. To address the challenge of discovery and optimization of HPs in huge chemical and compositional spaces of possible candidates, this perspective discusses a comprehensive strategy for screening HPs through automated high-throughput and combinatorial synthesis techniques.
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