Browsing by Subject "Molecular weight"

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    Expression of a Novel Myosin Light Chain Kinase in Embryonic Tissues and Cultured Cells
    (Elsevier, 1995) Gallagher, Patricia J.; Garcia, Joe G. N.; Herring, B. Paul; Anatomy, Cell Biology and Physiology, School of Medicine
    A novel, 208-kDa myosin light chain kinase (MLCK) distinct from smooth muscle and non-muscle MLCK has been identified by cross-reaction to two antibodies raised against smooth muscle MLCK. Additional antibodies directed against the amino and carboxyl termini of the smooth muscle MLCK do not react with the 208-kDa MLCK, suggesting these regions are distinct. 208-kDa MLCK phosphorylates 20-kDa myosin light chains in a Ca2+/calmodulin-dependent manner, consistent with it being a member of the MLCK family. Expression of 208-kDa MLCK and smooth muscle MLCK appears to be inversely regulated, with 208-kDa MLCK being most abundant during early development and declining at birth. In contrast, expression of smooth muscle MLCK is relatively low early during development and increases to become the predominant MLCK detected in all adult smooth and non-muscle tissues. The developmental expression pattern of the 208-kDa MLCK suggests this form be named, embryonic MLCK.
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    Structure-Based Design of Active-Site-Directed, Highly Potent, Selective, and Orally Bioavailable Low-Molecular-Weight Protein Tyrosine Phosphatase Inhibitors
    (American Chemical Society, 2022) He, Rongjun; Wang, Jifeng; Yu, Zhi-Hong; Moyers, Julie S.; Michael, M. Dodson; Durham, Timothy B.; Cramer, Jeff W.; Qian, Yuewei; Lin, Amy; Wu, Li; Noinaj, Nicholas; Barrett, David G.; Zhang, Zhong-Yin; Biochemistry and Molecular Biology, School of Medicine
    Protein tyrosine phosphatases constitute an important class of drug targets whose potential has been limited by the paucity of drug-like small-molecule inhibitors. We recently described a class of active-site-directed, moderately selective, and potent inhibitors of the low-molecular-weight protein tyrosine phosphatase (LMW-PTP). Here, we report our extensive structure-based design and optimization effort that afforded inhibitors with vastly improved potency and specificity. The leading compound inhibits LMW-PTP potently and selectively (Ki = 1.2 nM, >8000-fold selectivity). Many compounds exhibit favorable drug-like properties, such as low molecular weight, weak cytochrome P450 inhibition, high metabolic stability, moderate to high cell permeability (Papp > 0.2 nm/s), and moderate to good oral bioavailability (% F from 23 to 50% in mice), and therefore can be used as in vivo chemical probes to further dissect the complex biological as well as pathophysiological roles of LMW-PTP and for the development of therapeutics targeting LMW-PTP.