A5084924463- Angiogenesis and VEGF in Cancer
- HER2/EGFR in Cancer Research
- Cancer Treatment and Pharmacology
- Medicinal Plant Pharmacodynamics Research
- Flavonoids in Medical Research
- Cell Adhesion Molecules Research
- Bacteriophages and microbial interactions
- Heat shock proteins research
- Fungal and yeast genetics research
- Enzyme Structure and Function
- Cancer therapeutics and mechanisms
- Multiple Myeloma Research and Treatments
- Chemokine receptors and signaling
- Endoplasmic Reticulum Stress and Disease
- Neuroscience and Neural Engineering
- RNA and protein synthesis mechanisms
- Retinoids in leukemia and cellular processes
- Glycosylation and Glycoproteins Research
- Estrogen and related hormone effects
- Acute Myeloid Leukemia Research
- Protein Structure and Dynamics
- Monoclonal and Polyclonal Antibodies Research
- Viral Infectious Diseases and Gene Expression in Insects
- Pluripotent Stem Cells Research
- Hepatitis B Virus Studies
Glykos (Finland)
2010-2024
University of Helsinki
1979-2011
Czech Academy of Sciences, Institute of Biotechnology
2004
Biotechnology Institute
2004
Helsinki Institute of Physics
1999
Biocenter Finland
1997
University of Oulu
1979
The filamentous fungus Trichoderma reesei has tremendous capability to secrete proteins. Therefore, it would be an excellent host for producing high levels of therapeutic proteins at low cost. Developing a produce sensitive requires that protease secretion is drastically reduced. We have identified 13 major secreted proteases are related degradation antibodies, interferon alpha 2b, and insulin like growth factor. observed were aspartic, glutamic, subtilisin-like, trypsin-like proteases....
Saccharomyces cerevisiae cells grown at physiological temperature 24°C require preconditioning 37°C to acquire tolerance towards brief exposure 48–50°C. During preconditioning, the cytosolic trehalose content increases remarkably and in absence of synthesis yeast cannot thermotolerance. It has been speculated that protects proteins membranes under environmental stress conditions, but recently it was shown assist Hsp104 chaperone refolding heat‐damaged cytosol. We have demonstrated...
Bacteriophage PRD1 is a lipid‐containing virus that infects variety of Gram‐negative bacteria, including Escherichia coli. The phage lyses its host by virtue virally‐encoded lytic enzyme, the synthesis which has been assigned to gene XV on basis complementation analysis and experiments with mutant phages. We report here cloning into an expression plasmid purification product, protein P15, near homogeneity. purified identified N‐terminal sequence analysis, showed strong activity against...
Summary Thermal insult at 50°C causes protein denaturation in yeast, but the cells survive if preconditioned 37°C. Survival depends on refolding of heat‐denatured proteins. Refolding cytoplasmic proteins requires Hsp104, expression which increases several‐fold upon shift from physiological temperature 24°C to We describe here a novel type regulation designated delayed upregulation (DUR). When Saccharomyces cerevisiae grown 24°C, 37°C and treated briefly were shifted back Hsp104 was...
Antibody-drug conjugates (ADC) have shown impressive clinical activity with approval of many agents in hematologic and solid tumors. However, challenges remain both efficacy safety ADCs. This study describes novel trastuzumab-auristatin the hydrophilic monomethylauristatin E (MMAE) prodrug MMAU, optimization a glycopeptide linker leading to wider therapeutic window. Trastuzumab was conjugated auristatin payloads via series linkers using stabilized maleimide handle. The ADCs were...
CD33 (Siglec-3) is a cell surface receptor expressed in approximately 90% of acute myeloid leukemia (AML) blasts, making it an attractive target for therapy AML. Although previous CD33-targeting antibody-drug conjugates (ADC) like gemtuzumab ozogamicin (GO, Mylotarg) have shown efficacy AML treatment, they suffered from toxicity and narrow therapeutic window. This study aimed to develop novelADCwith improved tolerability wider GLK-33 consists the anti-CD33 antibody lintuzumab eight mavg-MMAU...
Severe heat stress causes protein denaturation in various cellular compartments. If Saccharomyces cerevisiae cells grown at 24°C are preconditioned 37°C, proteins denatured by subsequent exposure to 48–50°C can be renatured when the allowed recover 24°C. Conformational repair of vital is essential for survival, because gene expression transiently blocked after thermal insult. Refolding cytoplasmic requires Hsp104 chaperone, and refolding lumenal endoplasmic reticulum (ER) Hsp70 homologue...
Heterologous glycoproteins usually do not fold properly in yeast cells and fail to leave the endoplasmic reticulum. Here we show that Hsp150Δ polypeptide carrier promoted proper folding secretion of catalytic ectodomain rat α2,3-sialyltransferase (ST3Ne) Pichia pastoris.The efficiency P. pastoris Saccharomyces cerevisiae was at least as high MFα carrier. Most Hsp150Δ-ST3Ne MFα-ST3Ne remained noncovalently attached cell wall via ST3Ne portion. The strength HSP150promoter found be comparable...
Assembly factors, proteins assisting the formation of viral structures, have been found in many systems. The gene encoding assembly factor P17 bacteriophage PRD1 has cloned and expressed Escherichia coli . acts late phage assembly, after capsid protein folding multimerization, sorting membrane occurred. purified to near homogeneity. It is a tetrameric displaying rather high heat stability. largely an α‐helical conformation possesses putative leucine zipper which not essential for function,...
<p>Ex vivo cytotoxicity assays with leukemia blast samples.</p>
<p>Supplementary Methods and Results</p>
<p>GLK-33 binding and internalization to CD33+ cells.</p>
<p>Characterization of overconjugated GLK-33 batch in rat tolerability and toxicokinetic study.</p>
<p>Supplementary Methods and Results</p>
<p>Characterization of LN-mcvc-MMAE DAR4 (lintuzumab vedotin).</p>