Disease relevance of cycloleucine

• Cycloleucine was administered as a single dose intraperitoneally (2 mg/g body weight) to young mice aged 21 d and adults aged 6 or 10 wks [1].
• Particles of reduced infectivity and deficient in envelope glycoproteins are produced in cycloleucine-treated B77 avian sarcoma virus-infected chicken embryo fibroblasts [2].
• Cycloleucine toxicity is correlated with a block of SAM biosynthesis and nucleic acids methylations [3].
• Alteration of the 5' terminal caps of the mRNAs of vesicular stomatitis virus by cycloleucine in vivo [4].
• Synergistic suppression of the hyperacute form of experimental allergic encephalomyelitis by tilorone and cycloleucine [5].

High impact information on cycloleucine

• Guaran in the perfusate (1-7 g/L) inhibited small intestinal absorption of actively transported compounds, such as alpha-methyl-D-glucoside, cycloleucine, and taurocholate, and also of the passively permeating solutes 2-deoxy-D-glucose and urea [6].
• The evolution of an experimental distal motor axonopathy. Physiological studies of changes in neuromuscular transmission caused by cycloleucine, an inhibitor of methionine adenosyltransferase [7].
• The in vivo stability of methylated and unmethylated cytochrome c in Saccharomyces cerevisiae was studied by pulse-labeling the hemoproteins with [methyl-3H]-methionine and/or [2-14C]methionine and following the fate of these proteins under anaerobiosis and in the presence of cycloleucine [8].
• Under conditions where 40 mM cycloleucine is present, internal N-6-methyladenosine and 5'-terminal can 2'-O-ribose methylations of poly(A)+ RNA are inhibited greater than 90% [9].
• The poly(A)+ RNA synthesized in cycloleucine-treated cells is transported from the nucleus to the cytoplasm and associates with polyribosomes at rates comparable to poly(A)+ RNA in untreated cells [9].

Chemical compound and disease context of cycloleucine

• When cells are grown in a medium containing 10 micron methionine, cycloleucine is an inhibitor of cell proliferation; high concentrations of methionine are able to withdraw this inhibition suggesting that cycloleucine toxicity is related to methionine metabolism [3].
• Vesicular stomatitis virus mRNA methylation in vivo: effect of cycloleucine, an inhibitor of S-adenosylmethionine biosynthesis, on viral transcription and translation [10].
• The injection of cycloleucine (1-aminocyclopentanecarboxylic acid (ACPC) into rats produces a hyperexcretion of dibasic amino acids and cystine, an aberration resembling cystinuria [11].
• Comparison of doxorubicin with cycloleucine in the treatment of sarcomas [12].

Biological context of cycloleucine

• The role of RNA methylations in the control of tRNA production and utilization for protein biosynthesis has been investigated through a study of the effects in vivo of cycloleucine a specific and potent inhibitor of S adenosyl-methionine mediated methylation [13].
• During the cycloleucine treatment, the rate of biosynthesis of hnRNA and its subsequent polyadenylation were only slightly reduced as compared with untreated cells [14].
• We have found that cycloleucine, ethionine, and 5'-deoxy-5'-methylthioadenosine (MTA) are all effective as inhibitors of enzymatic DNA methylation, but that there is no differential effect between the delayed and non-delayed methylation reactions [15].
• The two amino acids showed markedly different kinetics of exit, that of AIB being monoexponential while that of cycloleucine was biexponential [16].
• The actions of cycloleucine on progression in the cell cycle and DNA, RNA and protein biosynthesis are studied [3].

Anatomical context of cycloleucine

• Distal motor axonopathy and central nervous system myelin vacuolation caused by cycloleucine, an inhibitor of methionine adenosyltransferase [1].
• Hepatocytes concentrated alpha-aminoisobutyric acid to a 3-fold higher degree than cycloleucine [17].
• Cycloleucine (CL), an inhibitor of methionine adenosyltransferase, has previously been used to produce an experimental model of subacute combined degeneration of the spinal cord [1].
• Biosynthesis and utilization of extensively undermethylated poly(A)+ RNA in CHO cells during a cycloleucine treatment [14].
• Insulin also failed to stimulate cellular uptake of cycloleucine in skeletal muscle from acutely uremic animals [18].

Associations of cycloleucine with other chemical compounds

• The role of RNA methylations in the control of mRNA maturation and incorporation into polysomes has been investigated through a study of the effects in vivo of cycloleucine, a specific inhibitor of S-adenosyl-methionine mediated methylation [14].
• This report compares the effect of insulin on in vitro 14C alpha-amino isobutyric acid and cycloleucine uptake by skeletal muscle from uremic and control rats [18].
• The uptake of leucine and cycloleucine by the L system was quite different during the cell cycle [19].
• We used cycloleucine (CL), which prevents the conversion of methionine to SAMe by inhibiting ATP-l-methionine-adenosyltransferase (MAT), to characterize the lipid and protein changes induced in peripheral nerve and brain myelin in rats during development [20].
• Uptake of lysine was normal in CF patients whereas that of phenylalanine and cycloleucine was reduced as compared to control subjects [21].

Gene context of cycloleucine

• This study describes the synthesis and some pharmacological properties of eight new analogues of arginine vasopressin (AVP) substituted at position 2 or 3 with cycloleucine (1-aminocyclopentane-1-carboxylic acid, Apc) [22].
• Growth hormone added to the medium during the entire 65-min perfusion at a concentration of 1 mug per ml caused a 30% increase in the cycloleucine distribution ratio [23].
• There was a differential sensitivity towards the inhibition by cycloleucine between the expressed PfSAMS and the human hepatic SAMS with K(i) values of 17 and 10 mM, respectively [24].
• The influence of cycloleucine on the amino acid uptake was not specific either to the amino acid concerned or to a particular transport system, since the three neutral amino acid-transport systems, A, ASC and L, were involved in these experiments [25].
• The amount of dihydrofolate reductase protein produced from the transcripts of the cycloleucine treated cells was 20% less than untreated transcripts [26].

Analytical, diagnostic and therapeutic context of cycloleucine

• Accumulation of cycloleucine was linear for only about 20 min of perfusion and then plateaued [23].
• After treatment with 2 and 5 mg/ml of cycloleucine, internal m6As were reduced by 10- and 100-fold, respectively [27].
• The analogues of oxytocin and [1-penicillamine]oxytocin, containing a cycloleucine (Cle) residue in position 2 or 8, were investigated by means of circular dichroism measurements in different solvents, and the results examined in terms of their biological activities [28].

References