Cyclo(L-Leu-L-Trp)

Cyclo(L-Leu-L-Trp) is a diketopiperazine metabolite originally isolated from Penicillium.¹ It is active against various bacteria (MICs = 125-1000 µg/ml) and fungi (MICs = 8-64 µg/ml), and it inhibits the production rate of hydroxy radicals in an electron spin resonance (ESR) spectroscopy-based assay (IC₅₀ = 1.8 µM).^2,3 Cyclo(L-Leu-L-Trp) is a bitter tastant that can rapidly permeate rat taste cell membranes ex vivo when used at a concentration of 1 mM.⁴ It also acts as a melatonin receptor agonist in X. laevis melanophores, inhibiting cAMP accumulation when used at a concentration of 20 µM, an effect that is blocked by the melatonin receptor antagonist luzindole (Item No. 15998).⁵

WARNING This product is not for human or veterinary use.

1. Solov'eva, T.F., Baskunov, B.P., Nefedova, M.Y., et al. Biosynthesis of leucyl-tryptophanyl-diketopiperazine by a culture of Penicillium aurantio-virens and the characteristics of its production. Mikrobiol. 58(3), 393-399 (1989).

2. Kumar, S.N., Mohandas, C., and Nambisan, B. Purification, structural elucidation and bioactivity of tryptophan containing diketopiperazines, from Comamonas testosteroni associated with a rhabditid entomopathogenic nematode against major human-pathogenic bacteria. Peptides 53(2014), 48-58 (2014).

3. Furukawa, T., Akutagawa, T., Funatani, H., et al. Cyclic dipeptides exhibit potency for scavenging radicals. Bioorg. Med. Chem. 20(6), 2002-2009 (2012).

4. Naim, M., Nir, S., Spielman, A.I., et al. Hypothesis of receptor-dependent and receptor-independent mechanisms for bitter and sweet taste transduction: Implications for slow taste onset and lingering aftertaste. Chemistry of Taste 825, 2–17 (2002).

5. Zubare-Samuelov, M., Peri, I., Tal, M., et al. Some sweet and bitter tastants stimulate inhibitory pathway of adenylyl cyclase via melatonin and α2-adrenergic receptors in Xenopus laevis melanophores. Am. J. Physiol. Cell Physiol. 285(5), C1255-1262 (2003).