The mechanism of proteolysis by serine proteases is a reasonably well-understood process. Typically, a histidine residue acting as a general base deprotonates the catalytic serine residue and the hydrolytic water molecule. We disclose here, the use of an unnatural d-amino acid as a strategic residue in P1 position, designed de novo based on the architecture of the protease catalytic site to impede the catalytic histidine residue at the stage of acyl-enzyme intermediate.
View Article and Find Full Text PDFDesigner fluoropeptidomimetics as protease inhibitors are revealed. The key peptidomimetic region in the inhibitors contains a '-CHF-S-' moiety and is designed to mimic the tetrahedral oxyanion species during the hydrolysis of a peptide bond. Designed fluoropeptidomimetics in aqueous methanol slowly (in several hours to days) yielded the corresponding methyl ether and/or the oxazole derivatives after cyclization.
View Article and Find Full Text PDFMammaglobin-A is exclusively expressed by breast cancer cells. Thus, mammaglobin-A-specific T cell immune responses may be useful for the design of new breast cancer-specific immunotherapies. We show herein that CD8+ T cells generated against recombinant mammaglobin-A-pulsed dendritic cells display a marked cytotoxic activity against mammaglobin-A-positive breast cancer cell lines.
View Article and Find Full Text PDFMammaglobin-A is highly overexpressed in breast cancer cell lines and primary breast tumors. This pattern of expression is restricted to mammary epithelium and metastatic breast tumors. Thus, mammaglobin-A-specific T cell immune responses may provide an important approach for the design of breast cancer-specific immunotherapy.
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