Cycloleucine
(Synonyms: 环亮氨酸) 目录号 : GC61751
Cycloleucine是一种S-腺苷甲硫氨酸介导的甲基化的特异性抑制剂。Cycloleucine是NMDA受体甘氨酸变构位点的拮抗剂，Ki值为600μM。Cycloleucine在体外也是ATP:L-蛋氨酸-S-腺苷基转移酶的竞争性抑制剂。Cycloleucine具有抗焦虑和抑制细胞作用。
Cas No.:52-52-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cycloleucine is a specific inhibitor of S-adenosyl-methionine mediated methylation. Cycloleucine is antagonist of NMDA receptor associated glycine receptor, with a Ki of 600 μM. Cycloleucine is also a competitive inhibitor of ATP: L-methionine-S-adenosyl transferase in vitro. Cycloleucine has anxiolytic and cytostatic effects[1][2][3][4].
Cycloleucine (4-40 mM; 3 h) blocks internal methylation of viral RNA in B77 transformed chick embryo fibroblasts[5].Cycloleucine (40 mM; 24 h) blocks the formation of both m6A and the penultimate Gm in B77 38S RNA subunits by greater than 90%[5].Cytostatic (10 µg/mL) inhibits the viability human KB and mouse L1210s leukemia cell lines[5].
Cycloleucine (0.5-4 µg; intracerebroventrical injection) increases time spent in open arms, open arm entries, and extreme arrivals in rats[3]. Animal Model: Male rats bilaterally cannulated into the nucleus accumbens septi (NAS)[3]
[1]. Hood WF, et, al. 1-Aminocyclobutane-1-carboxylate (ACBC): a specific antagonist of the N-methyl-D-aspartate receptor coupled glycine receptor. Eur J Pharmacol. 1989 Feb 28;161(2-3):281-2. [2]. Caboche M, et, al. RNA methylation and control of eukaryotic RNA biosynthesis. Effects of cycloleucine, a specific inhibitor of methylation, on ribosomal RNA maturation. Eur J Biochem. 1977 Mar 15;74(1):19-29. [3]. Gargiulo API, et, al. Effects of Cycloleucine in the Nucleus Accumbens Septi on the Elevated plus Maze Test in Rats. Neuropsychobiology. 2020;79(3):191-197. [4]. Du? D, et, al. Cytostatic activity in vitro of cycloleucine, aspartic acid and glutamic acid phosphonic analogues. Arch Immunol Ther Exp (Warsz). 1980;28(3):433-8. [5]. Dimock K, et, al. Cycloleucine blocks 5'-terminal and internal methylations of avian sarcoma virus genome RNA. Biochemistry. 1978 Aug 22;17(17):3627-32.
| Cas No. | 52-52-8 | SDF | |
| 别名 | 环亮氨酸 | ||
| Canonical SMILES | O=C(O)C1(CCCC1)N | ||
| 分子式 | C6H11NO2 | 分子量 | 129.16 |
| 溶解度 | Water: 50 mg/mL (387.12 mM); DMSO: < 1 mg/mL (ultrasonic) (insoluble or slightly soluble) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 7.7423 mL | 38.7117 mL | 77.4234 mL |
| 5 mM | 1.5485 mL | 7.7423 mL | 15.4847 mL |
| 10 mM | 0.7742 mL | 3.8712 mL | 7.7423 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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1. 首先保证母液是澄清的；
2.
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Transcriptome analysis of the inhibitory effect of Cycloleucine on myogenesis
Poult Sci 2022 Dec;101(12):102219.PMID:36308813DOI:10.1016/j.psj.2022.102219.
N6-Methyladenosine (m6A) has been reported to involve and play an important role in various biological activities but seldom in poultry myogenesis. Cycloleucine usually functions as a nucleic acid methylation inhibitor, the inhibition efficiency of Cycloleucine at the m6A level and corresponding dynamic changes of poultry muscle cells remain unknown. In this study, we aim to find out the effect of Cycloleucine on the total N6-Methyladenosine level and its molecular mechanism for regulating myogenesis. A total of 745 differentially expressed genes (DEGs) were obtained by 10 mM, 20 mM, and 30 mM of Cycloleucine treatment compared with 0 mM treatment. DEGs in 10 mM Cycloleucine were significantly enriched in the biological process of skeletal muscle and satellite cell proliferation and differentiation, DEGs in 20 and 30 mM Cycloleucine were enriched in some metabolic and biosynthetic processes. The trend analysis showed that 85% of all DEGs were significantly clustered into 4 files, among them 59% DEGs were dose-dependent and 26% were dose-independent, 52% DEGs were in downtrend and 33% DEGs were in uptrend. Also, the Cycloleucine treatment could trigger cell cycle arrest in the G1 phase and depress myoblast cell proliferation and inhibit myotube formation. In conclusion, Cycloleucine could continuously reduce the m6A level of myoblast cells, depress myoblast cell proliferation and inhibit myotube formation.
Effects of Cycloleucine in the Nucleus Accumbens Septi on the Elevated plus Maze Test in Rats
Neuropsychobiology 2020;79(3):191-197.PMID:31927553DOI:10.1159/000505069.
Introduction: In recent years, an important number of studies have emphasized the psychopharmacological actions of Cycloleucine (1-aminocyclopentanecarboxylic acid) acting on the NR1 subunit (glycine allosteric site) of NMDA (N-methyl-D-aspartic acid) receptor. We studied the effects of its injection in an anxiety test. Methods: The elevated plus maze test was used. Male rats bilaterally cannulated into the nucleus accumbens septi (NAS) were employed. Rats were divided into 5 groups that received either 1 µL injections of saline or Cycloleucine (0.5, 1, 2, or 4 µg) 15 min before testing. Results: Time spent in the open arm was significantly increased by Cycloleucine treatment with all doses (1 and 2 µg, p < 0.05; 0.5 and 4 µg, p < 0.01), like number of extreme arrivals (0.5 and 1 µg, p < 0.05; 2 µg, p < 0.01; and 4 µg, p < 0.001). Open arm entries were increased by the highest dose only (4 µg, p < 0.01). Discussion/conclusion: Present results show no difference between all doses in the time spent in the open arm, suggesting an indirect, noncompetitive action of the drug. The increase in extreme arrivals and open arm entries suggests a dose influence in these parameters. We conclude that Cycloleucine influence on the NMDA receptors within NAS leads to anxiolytic-like effects and behavioral disinhibition, which once more confirms the involvement of NAS in anxiety processing.
Cycloleucine blocks 5'-terminal and internal methylations of avian sarcoma virus genome RNA
Biochemistry 1978 Aug 22;17(17):3627-32.PMID:210799DOI:10.1021/bi00610a032.
Cycloleucine, a competitive inhibitor of ATP: L-methionine S-adenosyltransferase in vitro, has been used to reduce intracellular concentrations of S-adenosylmethionine and by this means to inhibit virion RNA methylation in chicken embryo cells that are infected with B77 avian sarcoma virus. Under conditions of Cycloleucine treatment, where virus production as measured by incorporation of radioactive precursors or by number of infectious particles is not significantly affected, the internal m6A methylations of the avian sarcoma virus genome RNA are inhibited greater than 90%. The predominant 5'-terminal structure in viral RNA produced by treated cells in m7G(5')pppG (cap zero) rather than m7G-(5')pppGm (cap 1). It appears from these results that internal m6A and penultimate ribose methylations are not required for avian sarcoma RNA synthesis and function. Furthermore, these methylations are apparently not required for transport of genome RNA to virus assembly sites. The insensitivity of the 5'-terminal m7G methylation to inhibition by Cycloleucine suggests that the affinity of S-adenosylmethionine for 7-methylguanosine methyltransferase is significantly greater than for the 2'-0-methyltransferases or the N6-methyltransferases.
Experimental cystinuria: the Cycloleucine model. II. Amino acid efflux from intestinal and renal tissues
Metabolism 1978 Nov;27(11):1613-25.PMID:703604DOI:10.1016/0026-0495(78)90284-6.
Loading and unloading experiments using intestinal sacs and renal cortex slices were undertaken to ascertain the role of amino acid efflux in cycloleucine-induced amino-aciduria. The presence of Cycloleucine, lysine, or valine on the luminal or antiluminal side of the intestine caused an increased leakage of [14C] Cycloleucine, [14C] lysine, and [35S] cystine from the tissue. Similar results were obtained when using kidney cortex slices, except for cystine efflux. The latter phenomenon was inhibited by Cycloleucine and lysine. Data, also obtained with renal cortex slices, suggest that cystine and cysteine are recognized by different transport sites although one (the oxidized form) may be typically extracellular and the other (the reduced form), intracellular. A comparison of these data with previous works done in our laboratory shows that Cycloleucine affects efflux less than influx and further suggests that in rats given Cycloleucine, renal transport is impaired only at the brush border level for cystine and at both luminal and antiluminal membranes for dibasic amino acids.
Cycloleucine uptake in the brainstem of thiamine-deficient rats
Acta Neuropathol 1976 Sep 15;36(1):47-56.PMID:970113DOI:10.1007/BF00685147.
Immature female rats were subjected to acute dietary deficiency of thiamine. An autoradiographic method was used in the semi-quantitative determination of concentration of 1-aminocyclopentane-1-carboxylic acid-carboxylic-14C (Cycloleucine) in brainstem regions after intravenous administration of tracer quantities. The time course of tissue concentrations was followed and compared with that of normal and isocaloric control animals. Our data indicate that thiamine deficiency of sufficient magnitude to induce brainstem lesions has an effect on the transport of Cycloleucine. The initial 2 min values in the nuclear areas are appreciably reduced whereas the 6 min values are significantly elevated as compared with controls; no change was demonstrated in the white matter of the inferior cerebellar peduncle. The effect on transport appears to be more on the mechanism of efflux than of influx in terms of blood brain barrier function.