Publications by authors named "A Koide"
Mirror-image proteins, composed of D-amino acids, are an attractive therapeutic modality, as they exhibit high metabolic stability and lack immunogenicity. Development of mirror-image binding proteins is achieved through chemical synthesis of D-target proteins, phage display library selection of L-binders and chemical synthesis of (mirror-image) D-binders that consequently bind the physiological L-targets. Monobodies are well-established synthetic (L-)binding proteins and their small size (~90 residues) and lack of endogenous cysteine residues make them particularly accessible to chemical synthesis.
View Article and Find Full Text PDFOncogenic mutations in the extracellular domain (ECD) of cell-surface receptors could serve as tumor-specific antigens that are accessible to antibody therapeutics. Such mutations have been identified in receptor tyrosine kinases including HER2. However, it is challenging to selectively target a point mutant, while sparing the wild-type protein.
View Article and Find Full Text PDFBackground: The inability of biologics to pass the plasma membrane prevents their development as therapeutics for intracellular targets. To address the lack of methods for cytosolic protein delivery, we used the type III secretion system (T3SS) of Y. enterocolitica, which naturally injects bacterial proteins into eukaryotic host cells, to deliver monobody proteins into cancer cells.
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- - The RAS family GTPases are a key group of oncogenes frequently mutated in human cancers, with mutations found in about 20% of tumors, particularly NRAS mutations present in about 25% of melanomas.
- - Current therapies have targeted KRAS mutations effectively, but there is a significant lack of treatments specifically aimed at NRAS, making it a critical area for developing new cancer therapies.
- - This study introduces a new monobody that can bind to both forms of NRAS and inhibit its signaling, offering a promising direction for creating selective inhibitors and potential therapeutics for NRAS and BRAF-mutant melanomas.
Objectives: The Cancer Control Act requires the maintenance of regional cooperation pathways (RCP) for cancer treatment. In 2008, we started RCP for early detection of new gastric cancer after endoscopic submucosal dissection (ESD). In gastric cancer treatment, RCP after surgical resection had been widely used, but little is known about RCP after ESD.
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