A5037938392- Monoclonal and Polyclonal Antibodies Research
- Radiopharmaceutical Chemistry and Applications
- Photosynthetic Processes and Mechanisms
- HER2/EGFR in Cancer Research
- Metal-Catalyzed Oxygenation Mechanisms
- Glycosylation and Glycoproteins Research
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Asymmetric Hydrogenation and Catalysis
- CAR-T cell therapy research
- Organophosphorus compounds synthesis
- Medical Imaging Techniques and Applications
- Advanced Biosensing Techniques and Applications
- Medical Imaging and Pathology Studies
- Biochemical and Structural Characterization
- Synthesis and Biological Evaluation
- Neuroendocrine Tumor Research Advances
- Peptidase Inhibition and Analysis
- Click Chemistry and Applications
- Protein Degradation and Inhibitors
- Enzyme Structure and Function
- Nitric Oxide and Endothelin Effects
- Receptor Mechanisms and Signaling
- Chemical Synthesis and Analysis
- Healthcare Systems and Public Health
KTH Royal Institute of Technology
2015-2025
AlbaNova
2016-2025
AstraZeneca (Sweden)
2023
Stockholm University
2004-2011
University of Pennsylvania
2007
University of Gothenburg
2004
Affibody molecules are small (7 kDa), non-immunoglobulin scaffold proteins with a potential as targeting agents for radionuclide imaging of cancer.However, high renal re-absorption prevents their use therapy residualizing radiometals.We hypothesized that the Affibody-based peptide nucleic acid (PNA)-mediated pretargeting would enable higher accumulation radiometals in tumors than kidneys.To test this hypothesis, we designed an Affibody-PNA chimera Z HER2:342 -SR-HP1 containing 15-mer HP1 PNA...
Affibody molecules are small proteins engineered using a nonantibody scaffold. Radiolabeled excellent imaging probes, but their application to radionuclide therapy has been prevented by high renal reabsorption. The aim of this study was test the hypothesis that Affibody-based peptide nucleic acid (PNA)–mediated pretargeted human epidermal growth factor receptor 2 (HER2)–expressing cancer extends survival without accompanying toxicity. <b>Methods:</b> A HER2-targeting molecule ligated with an...
A promising strategy to enable patient stratification for targeted therapies is monitor the target expression in a tumor by radionuclide molecular imaging. Affibody molecules (7 kDa) are nonimmunoglobulin scaffold proteins with 25-fold smaller size than intact antibodies. They have shown an apparent potential as imaging probes both preclinical and clinical studies. Earlier, we found that hepatic uptake can be reduced incorporation of negatively charged purification tags at N-terminus...
In radioimmunotherapy, the contrast between tumor and normal tissue can be improved by using a pretargeting strategy with primary targeting agent, which is conjugated to recognition tag, secondary radiolabeled molecule binding specifically tag. The injected after agent has accumulated in designed have favorable biodistribution profile, fast clearance from blood low uptake tissues. this study, we evaluated two complementary peptide nucleic acid (PNA)-based probes for specific high-affinity...
This report describes a model protein specifically tailored to electrochemically study the reduction potential of tyrosine radicals as function pH. The system is based on 67-residue α(3)Y three-helix bundle. contains single buried at position 32 and displays structural properties inherent protein. present presents differential pulse voltammograms obtained from both acidic (pH 5.6) alkaline 8.3) conditions. observed Faradaic response uniquely associated with Y32, shown by site-directed...
Novel building blocks are in constant demand during the search for innovative bioactive small molecule therapeutics by enabling construction of structure-activity-property-toxicology relationships. Complex chiral molecules containing multiple stereocenters an important component compound library expansion but can be difficult to access traditional organic synthesis. Herein, we report a biocatalytic process specific diastereomer amine block used drug discovery. A reductive aminase (RedAm) was...
Sodium-coupled monocarboxylate transporter 1 (SMCT1) is a membrane abundantly expressed in colon, kidney, thyroid, brain; and silenced cancer cells. It transports monocarboxylic acids with little specificity into Based on pulldown experiments, it was proposed that the scaffolding protein PDZ Domain Containing (PDZK1) regulates its surface expression increases SMCT1's transportation efficiency. Here, we performed pull-down assays, Surface Plasmon Resonance (SPR), Micro Scale Thermophoresis...
Designed ankyrin repeat proteins (DARPins) are a class of engineered scaffold (ESPs) with molecular weight approximately 15 kDa and picomolar affinity for tumor antigen targets. Proof-of-concept studies have demonstrated the potential DARPin radioimmunodiagnostics in humans. However, high accumulation activity kidneys limits their use conventional radionuclide therapy. A peptide nucleic acid (PNA)-based pretargeted approach was successfully applied to Affibody molecules, another ESP. We...
Pretargeting is a promising strategy to reach high imaging contrast in shorter time than by targeting with directly radiolabeled monoclonal antibodies (mAbs). One of problems pretargeting site-specific, reproducible and uniform conjugation recognition tags mAbs. To solve this issue we propose photoconjugation covalently couple tag mAb via photoactivatable Z domain. The Z-domain, 58-amino acid protein derived from the IgG-binding B-domain Staphylococcus aureus A, has well-characterized...
Antibody–DNA conjugates are powerful tools for DNA-assisted protein analysis. Growing usage of these methods demands efficient production high-quality conjugates. We developed an easy and fast synthesis route yielding covalent antibody–DNA with a defined conjugation site low batch-to-batch variability. utilize the Z domain from A, containing unnatural amino acid 4-benzoylphenylalanine (BPA) photoaffinity labeling antibodies' Fc region. Z(xBPA) domains C-terminally modified triple-glycine...
Affibody-mediated PNA-based pretargeting is a promising approach to radionuclide therapy of HER2-expressing tumors. In this study, we test the hypothesis that shortening PNA probes would increase tumor-to-kidney dose ratio. The primary probe ZHER2:342-SR-HP15 and complementary secondary HP16, HP17, HP18, containing 9, 12, 15 nucleobases, respectively, carrying 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator were designed, synthesized, characterized in vitro, labeled...
Treatment of patients with HER2-expressing tumors using the monoclonal antibody trastuzumab increases survival. The affibody-based peptide nucleic acid (PNA)-mediated pretargeted radionuclide therapy has demonstrated efficacy against xenografts in mice. Structural studies suggest that affibody molecules and bind to different epitopes on HER2. aim this study was test hypothesis a combination PNA-mediated treatment can extend survival compared monotherapies. <b>Methods:</b> Mutual interference...
The electrochemistry of 2,6-dimethylbenzoquinone (DMBQ) has been characterized for three different systems: DMBQ freely solvated in aqueous buffer; bound to a neutral, blocked cysteine (N-acetyl-L-cysteine methyl ester) and the resulting DMBQ-bCys compound small model protein denoted alpha(3)C. goal this study is detect characterize differences redox properties protein-ligated relative quinones. alpha(3)C used here tryptophan-32 cysteine-32 variant structurally defined alpha(3)W de novo (Dai...
Abstract Radionuclide molecular imaging of cancer-specific targets is a promising method to identify patients for targeted antibody therapy. Radiolabeled full-length antibodies however suffer from slow clearance, resulting in high background radiation. To overcome this problem, pretargeting system based on complementary peptide nucleic acid (PNA) probes has been investigated. The relies sequential injections primary, PNA-tagged and secondary, radiolabeled PNA probe, which are separated time,...
De novo protein design and electrochemistry were used to measure changes in the potential pKA of a phenol when its OH group is moved from solvent-exposed sequestered position. A "phenol rotation strategy" was adopted which phenols, containing SH position 4, 3, or 2 relative group, bound buried site. The α3C here tryptophan cysteine variant structurally defined α3W (Dai et al. (2002) J. Am. Chem. Soc. 124, 10952−10953). characteristics three mercaptophenol-α3C (MP-α3C) proteins are shown be...
Abstract Affibody molecules are engineered scaffold proteins, which demonstrated excellent binding to selected tumor-associated molecular abnormalities in vivo and highly sensitive specific radionuclide imaging of Her2-expressing tumors clinics. Recently, we have shown that peptide nucleic acid (PNA)-mediated affibody-based pretargeted therapy using beta-emitting 177 Lu extended significantly survival mice bearing human tumor xenografts. In this study, evaluated two approaches use positron...
The targeting of gastrin-releasing peptide receptors (GRPR) was recently proposed for targeted therapy, e.g., radiotherapy. Multiple and frequent injections peptide-based therapeutic agents would be required due to rapid blood clearance. By conjugation the GRPR antagonist RM26 (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) an ABD (albumin-binding domain), we aimed extend circulation peptides. synthesized conjugate DOTA-ABD-RM26 labelled with indium-111 evaluated in vitro vivo. stable PBS...
Affibody-mediated PNA-based pretargeting shows promise for HER2-expressing tumor radiotherapy. In our recent study, a 15-mer Z
The construction and characteristics of the stable well-structured α4W protein are described. 117-residue, single-chain has a molecular weight 13.1 kDa is designed to fold into four-helix bundle. Experimental characterization expressed purified shows 69.8 ± 0.8% helical content over 5.5–10.0 pH range. thermostable with TM > 355 K free energy unfolding as measured by chemical denaturation −4.7 kcal mol−1 at 25°C neutral pH. One-dimensional (1D) proton 2D 15N-HSQC spectra show narrow,...