Specific inhibitors for cathepsin L and cathepsin S have been developed with the help of computer-graphic modeling based on the stereo-structure. The common fragment, N-(L-trans-carbamoyloxyrane-2-carbonyl)-phenylalanine-dimethyla mide, is required for specific inhibition of cathepsin L. Seven novel inhibitors of the cathepsin L inhibitor Katunuma (CLIK) specifically inhibited cathepsin L at a ...

Inhibitors of histone deacetylases (HDACs) are a new class of anticancer agents that affect gene regulation. We had previously reported the first simple synthetic HDAC inhibitors with in vitro activity at submicromolar concentrations. Here, we present structure-activity data on modifications of a phenylalanine-containing lead compound including amino acid amides as well as variations of the ami...

The strong correlation between glyphosate uptake and growth inhibition of cultured carrot (Daucus carota L. cv Danvers) cells incubated in the presence of aspartate suggests that aspartate reverses glyphosate inhibition of growth primarily by reducing intracellular glyphosate concentration. Other compounds which reverse glyphosate inhibition of cell growth gave a range of effects on glyphosate ...

Compartmentalization of amino acid was investigated to define conditions required for accurate measurements of rates of protein synthesis in rat lungs perfused in situ. Lungs were perfused with Krebs-Henseleit bicarbonate buffer containing 4.5% (w/v) bovine serum albumin, 5.6mm-glucose, normal plasma concentrations of 19 amino acids, and 8.6-690mum-[U-(14)C]phenylalanine. The perfusate was equi...

We applied a nondestructive tracer technique, previously developed for measuring skeletal muscle protein turnover, to the measurement of myocardial protein turnover in vivo. During a continuous infusion of L-[ring-2,6-3H]phenylalanine to anesthetized, overnight-fasted dogs, we measured the uptake of radiolabeled phenylalanine from plasma and the release of unlabeled phenylalanine from myocardia...

Alkaline phosphatase (EC 3.1.3.1) isoenzymes in serum may be determined by multicomponent analysis of the enzyme activities in the presence of multiple inhibitors. To determine inhibition coefficients of the isoenzymes, we used multiple linear regression analysis to compare alkaline phosphatase activities in the presence of known inhibitors with electrophoretically determined isoenzyme activiti...

OBJECTIVE To demonstrate directly that highly reactive hydroxyl radicals (OH.) can be generated in patients with rheumatoid arthritis and contribute to joint damage, and to examine the ability of blood to cause OH. generation. METHODS The sensitive and specific technique of hydroxylation of aromatic compounds (salicylate and phenylalanine) was used to measure OH.. Synovial fluid and blood fro...

Phenylketonuria provides a human model for the study of the effect of phenylalanine on brain function. Although irreversible mental retardation is preventable through newborn diagnosis and dietary phenylalanine restriction, controversy exists regarding the effects of increased concentrations of phenylalanine in older patients. We have studied ten older, treated, phenylketonuric patients using a...

Insulin inhibits proteolysis in human muscle thereby increasing protein anabolism. In contrast, IGF-I promotes muscle protein anabolism principally by stimulating protein synthesis. As increases or decreases of plasma amino acids may affect protein turnover in muscle and also alter the muscle's response to insulin and/or IGF-I, this study was designed to examine the effects of insulin and IGF-I...