Prebiotic formation of cyclic dipeptides under potentially early Earth conditions

Jianxi Ying,Rongcan Lin,Yile Wu,Yufen Zhao,Pengxiang Xu,Yan Liu

doi:10.1038/s41598-018-19335-9

Jianxi Ying, Rongcan Lin + Show 4 more

Open Access

https://doi.org/10.1038/s41598-018-19335-9

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Journal: Scientific Reports	Publication Date: Jan 17, 2018
Citations: 39	License type: open-access

Affiliation: Xiamen University, Tsinghua University

Abstract

Cyclic dipeptides, also known as 2,5-diketopiperazines (DKPs), represent the simplest peptides that were first completely characterized. DKPs can catalyze the chiral selection of reactions and are considered as peptide precursors. The origin of biochemical chirality and synthesis of peptides remains abstruse problem believed to be essential precondition to origin of life. Therefore, it is reasonable to believe that the DKPs could have played a key role in the origin of life. How the formation of the DKPs through the condensation of unprotected amino acids in simulated prebiotic conditions has been unclear. Herein, it was found that cyclo-Pro-Pro could be formed directly from unprotected proline in the aqueous solution of trimetaphosphate (P3m) under mild condition with the yield up to 97%. Other amino acids were found to form proline-containing DKPs under the same conditions in spite of lower yield. During the formation process of these DKPs, P3m promotes the formation of linear dipeptides in the first step of the mechanism. The above findings are helpful and significant for understanding the formation of DKPs in the process of chemical evolution of life.

Highlights

As one of the simplest peptide derivatives in nature[1,2], Cyclic dipeptides, known as 2, 5-diketopiperazines (DKPs), which were ubiquitously observed in microorganism, plants and animals[3,4,5,6,7,8,9,10], have been found to have many biological activities[11,12,13,14] and chiral catalysis properties[15]
The results showed that six linear dipeptides were formed in the reactions with corresponding amino acids (Met, Phe, Gly, Ala, Val and Pro), while the remaining amino acids (Ser, Arg, His and Asp) did not form the corresponding dipeptides with the activation of P3m. (Table 1 and Supplementary Fig. S1)
The hydroxyproline could form the cyclic dipeptide, which was assigned by 1H NMR according to the previous report2. (Supplementary Fig. S8) These results suggest that pyrrole-containing α-amino acids are favored when reacted with P3m to form the cyclic dipeptides under the potentially prebiotic conditions

Summary

Introduction

As one of the simplest peptide derivatives in nature[1,2], Cyclic dipeptides, known as 2, 5-diketopiperazines (DKPs), which were ubiquitously observed in microorganism, plants and animals[3,4,5,6,7,8,9,10], have been found to have many biological activities (e.g., antiviral, antibiotic, anticancer)[11,12,13,14] and chiral catalysis properties[15]. L-amino acids (Met, Phe, Gly, Ala, Val, Pro, Ser, Arg, His and Asp) in aqueous solution at pH 10.7 and 35 °C for 7 days, respectively.

Results

Conclusion