1. Bioactive cyclic dipeptides
C Prasad Peptides. 1995;16(1):151-64. doi: 10.1016/0196-9781(94)00017-z.
Cyclic dipeptides are among the simplest peptide derivatives commonly found in nature. Most cyclic dipeptides found to date appear to have emerged as by-products of fermentation and food processing. However, many are endogenous to members of animal and plant kingdoms; these include cyclo(Pro-Leu), cyclo(Pro-Val), cyclo(Pro-Phe), cyclo(Ala-Leu), cyclo(Pro-Tyr), cyclo(Pro-Trp), and cyclo(His-Pro). Although the five cyclic dipeptides--cyclo(His-Pro), cyclo(Leu-Gly), cyclo(Tyr-Arg), cyclo(Asp-Pro), and cyclo(Pro-Phe)--exhibit interesting physiological and/or pharmacological activities in mammals, only one of these, cyclo(His-Pro), has been conclusively shown to be endogenous to mammals. On the other hand, cyclo(Leu-Gly), cyclo(Tyr-Arg), and cyclo(Asp-Pro) are structurally related to endogenous peptides Pro-Leu-Gly-NH2 (melanocyte-stimulating hormone release inhibiting factor), Tyr-Arg (kyotorphin), and Val-Pro-Asp-Pro-Arg (enterostatin), respectively, which may serve as precursor peptides. It needs to be determined, however, whether these peptides can indeed result from the processing of their respective precursors. In conclusion, it appears that cyclic dipeptides are a relatively unexplored class of bioactive peptides that may hold great promise for the future.
2. Comparative Metabolomics Reveals Fungal Conversion of Co-Existing Bacterial Metabolites within a Synthetic Aspergillus- Streptomyces Community
Yutong Shi, Yihan Ma, Jihua Wei, Yichao Ge, Wei Jiang, Shan He, Xiaodan Wu, Xiaoqin Zhang, Bin Wu Mar Drugs. 2021 Sep 19;19(9):526. doi: 10.3390/md19090526.
In nature, secondary metabolites have been proven to be the essential communication media between co-occurring microorganisms and to influence their relationship with each other. In this study, we conducted a metabolomics survey of the secondary metabolites of an artificial co-culture related to a hydrothermal vent fungal-bacterial community comprising Aspergillus sclerotiorum and Streptomyces and their reciprocal relationship. The fungal strain was found to increase the secretion of notoamides and the compound cyclo(Pro-Trp) produced by the actinomycetes strain was discovered to be the responsible molecule. This led to the hypothesis that the fungi transformed cyclo(Pro-Trp) synthesized by the actinomycetes as the biosynthetic precursors of notoamides in the chemical communication. Further analysis showed Streptomyces sp. WU20 was efficient in transforming amino acids into cyclo(Pro-Trp) and adding tryptophan as well as proline into the chemical communication enhanced the induction of the notoamide accumulation. Thus, we propose that the microbial transformation during the synthetic metabolically-mediated chemical communication might be a promising means of speeding up the discovery of novel bioactive molecules. The objective of this research was to clarify the mechanism of microbial transformation for the chemical communication. Besides, this research also highlights the utility of mass spectrometry-based metabolomics as an effective tool in the direct biochemical analysis of community metabolites.
3. Antimicrobial activity of selected cyclic dipeptides
M Graz, A Hunt, H Jamie, G Grant, P Milne Pharmazie. 1999 Oct;54(10):772-5.
Cyclic dipeptides are products of rational drug design, which may exhibit both antimicrobial and antitumor properties. The aim of this study was to investigate both the antimicrobial effects of the cyclic dipeptides cyclo(L-phenylalanyl-L-prolyl), cyclo(L-tyrosyl-L-prolyl), cyclo(L-tryptophanyl-L-prolyl) and cyclo(L-tryptophanyl-L-tryptophanyl) and the effects of these cyclic dipeptides on the gastrointestinal epithelium in vitro. Furthermore, a relevant solvent for the possible pharmaceutical application of the products was sought concurrently. The antimicrobial effect of the cyclic dipeptides was assayed using the Kirby-Bauer disc diffusion assay against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, Bacillus subtilis, Streptococcus pneumoniae, Candida albicans, Aspergillus niger and Penicillium notatum. The effect of the cyclic dipeptides on the gastrointestinal epithelium was assessed by changes in alkaline phosphatase expression of HT-29 cells. Cyclo(Pro-Trp) and cyclo(Phe-Pro) show broad spectrum antibacterial properties and cyclo(Trp-Pro) and cyclo(Trp-Trp) show broad spectrum antifungal properties. The maturation of the gastrointestinal cells was enhanced by cyclo(Phe-Pro), cyclo(Tyr-Pro), cyclo(Trp-Trp) and cyclo(Trp-Pro). The activity of these cyclic dipeptides thus indicates potential application of these compounds as pharmacological agents.
