Cycloleucine

Cycloleucine is a non-metabolizable amino acid formed by the cyclization of leucine[1]. It is a specific and reversible inhibitor of nucleic acid methylation and is widely used in biochemical experiments[1][3]. Cycloleucine has cytostatic, immunosuppressive, and antineoplastic activities[1]. It is a non-proteinogenic amino acid, meaning it is not naturally incorporated into proteins during translation[3].

Mechanism of Action

Cycloleucine acts as an antagonist of the NMDA receptor-associated glycine receptor, with a Ki of 600 μM[5]. It is also a competitive inhibitor of ATP: L-methionine-S-adenosyltransferase, which is involved in the synthesis of S-adenosylmethionine (SAM), a key methyl donor in various cellular methylation reactions[5].

Effects on Cell Metabolism and Development

Cycloleucine has been shown to lower SAM levels in control hepatocytes by inhibiting the conversion of 5'-methylthioadenosine to SAM through the methionine salvage pathway[3]. It has also been found to increase adipocyte growth by blocking methylation, leading to increased mRNA levels of N6-methyladenosine (m6A)[3]. Additionally, cycloleucine has been shown to negatively regulate porcine oocyte maturation and embryo development by modulating N6-methyladenosine and histone modifications[3].

Effects on Plant Growth and Development

Cycloleucine has been found to have toxic effects on plant cells, slowing plant growth and causing chlorosis and necrosis[4]. It has also been shown to affect the reproductive growth of plants, indicating that it directly affects the conversion and utilization of certain amino acids[4].

Availability and Synthesis

Cycloleucine is available for purchase from various suppliers, including Chem-Impex International, where it is offered as Fmoc-cycloleucine with a purity of ≥ 99% (HPLC)[2]. MedChemExpress also offers cycloleucine as an NMDA receptor antagonist[5].

In summary, cycloleucine is a non-metabolizable amino acid with specific and reversible inhibitory effects on nucleic acid methylation. It has been used in various biochemical experiments and has been found to have cytostatic, immunosuppressive, and antineoplastic activities. Its effects on cell metabolism and development, as well as its toxicity to plant cells, make it a compound of interest in various fields of research.

Citations:

[1] https://go.drugbank.com/drugs/DB04620

[2] https://www.chemimpex.com/fmoc-1-aminocyclopentane-1-carboxylic-acid

[3] https://en.wikipedia.org/wiki/Cycloleucine

[4] https://www.nature.com/articles/s41598-023-34509-w

[5] https://www.medchemexpress.com/cycloleucine.html