1. CETSA screening identifies known and novel thymidylate synthase inhibitors and slow intracellular activation of 5-fluorouracil.

    Nature Communications 7:11040 (2016) PMID 27010513 PMCID PMC4820820

    Target engagement is a critical factor for therapeutic efficacy. Assessment of compound binding to native target proteins in live cells is therefore highly desirable in all stages of drug discovery. We report here the first compound library screen based on biophysical measurements of intracellul...
  2. The cellular thermal shift assay for evaluating drug target interactions in cells.

    Nature Protocols 9(9):2100 (2014) PMID 25101824

    Thermal shift assays are used to study thermal stabilization of proteins upon ligand binding. Such assays have been used extensively on purified proteins in the drug discovery industry and in academia to detect interactions. Recently, we published a proof-of-principle study describing the implem...
  3. Monitoring drug target engagement in cells and tissues using the cellular thermal shift assay.

    Science 341(6141):84 (2013) PMID 23828940

    The efficacy of therapeutics is dependent on a drug binding to its cognate target. Optimization of target engagement by drugs in cells is often challenging, because drug binding cannot be monitored inside cells. We have developed a method for evaluating drug binding to target proteins in cells a...
  4. Construction of divalent anti-keratin 8 single-chain antibodies (sc(Fv)(2)), expression in Pichia pastoris and their reactivity with multicellular tumor spheroids.

    Journal of Immunological Methods 364(1-2):65 (2011) PMID 21093447

    Single-chain variable fragments (scFvs) are small monovalent recombinant antibody fragments that retain the specificity of their parent immunoglobulins. ScFvs are excellent building blocks for new and improved immunodiagnostic and therapeutic proteins. However, the monovalency and the rapid rena...
  5. Optimization of production of the anti-keratin 8 single-chain Fv TS1-218 in Pichia pastoris using design of experiments.

    Microbial Cell Factories 10:34 (2011) PMID 21575236 PMCID PMC3119184

    Optimization of conditions during recombinant protein production for improved yield is a major goal for protein scientists. Typically this is achieved by changing single crucial factor settings one at a time while other factors are kept fixed through trial-and-error experimentation. This approac...
  6. Localization of complexed anticytokeratin 8 scFv TS1-218 to HeLa HEp-2 multicellular tumor spheroids and experimental tumors.

    Cancer Biotherapy and Radiopharmaceuticals 25(4):455 (2010) PMID 20707717

    Recombinant single-chain fragment variable (scFv) antibodies with specificity to tumor antigens can be used to target tumors in vivo. The approach to use administration of complexes of idiotypic-anti-idiotypic scFvs when targeting tumors has not been tested earlier, and from a theoretical point ...
  7. Functional mapping of the anti-idiotypic antibody anti-TS1 scFv using site-directed mutagenesis and kinetic analysis.

    mAbs 2(6):662 (2010) PMID 21124071 PMCID PMC3011220

    Recombinant antibodies may be engineered to obtain improved functional properties. Functional mapping of the residues in the binding surfaces is of importance for predicting alterations needed to yield the desired properties. In this investigation, 17 single mutation mutant single-chain variable...
  8. Functional mapping and single chain construction of the anti-cytokeratin 8 monoclonal antibody TS1.

    Molecular Immunology 44(6):1075 (2007) PMID 16989900

    The anti-cytokeratin (CK) 8 monoclonal antibody (mab) TS1 has been shown to efficiently bind to CK8 expressed in carcinomas in vivo. The anti-idiotypic antibody of TS1, alphaTS1, can be used to regulate the tumor:non-tumor ratio of TS1 by clearing non-tumor binding TS1 from the circulation. If t...
  9. Functional mapping and single chain construction of the anti-cytokeratin 8 monoclonal antibody TS1

    Molecular Immunology 44(6):1075 (2007)

    The anti-cytokeratin (CK) 8 monoclonal antibody (mab) TS1 has been shown to efficiently bind to CK8 expressed in carcinomas in vivo. The anti-idiotypic antibody of TS1, αTS1, can be used to regulate the tumor:non-tumor ratio of TS1 by clearing non-tumor binding TS1 from the circulati...