Cyclic Dipeptides Formation From Linear Dipeptides Under Potentially Prebiotic Earth Conditions

Abstract

Cyclic dipeptides (DKPs) are peptide precursors and chiral catalysts in the prebiotic process. This study reports proline-containing DKPs that were spontaneously obtained from linear dipeptides under an aqueous solution. Significantly, the yields of DKPs were affected by the sequence of linear dipeptides and whether the reaction contains trimetaphosphate. These findings provide the possibility that DKPs might play a key role in the origin of life.

LC/MS Q-TOF Metabolomic Investigation of Amino Acids and Dipeptides in Pleurotus ostreatus Grown on Different Substrates

“…An in vitro experiment by Foltz highlighted a series of Pro-based dipeptides (Ile–Pro, Arg–Pro, Lys–Pro, and Gly–Pro) exhibiting a notable ACE inhibitory activity, with IC 50 values below 100 μM and with a high intestinal stability . Furthermore, Guo and co-workers reported the spontaneous cyclization of Pro-containing linear dipeptides in aqueous solution to give the corresponding cyclic diketopiperazines (DKPs), working as peptide/protein precursors or chiral catalysts . Due to their chiral, rigid, and functionalized structure, such cyclic dipeptides, most of which notably contain the Pro residue, could bind a large variety of receptors with high affinity, giving a wide spectrum of biological properties .…”

“…44 Furthermore, Guo and co-workers reported the spontaneous cyclization of Pro-containing linear dipeptides in aqueous solution to give the corresponding cyclic diketopiperazines (DKPs), working as peptide/protein precursors or chiral catalysts. 45 Due to their chiral, rigid, and functionalized structure, such cyclic dipeptides, most of which notably contain the Pro residue, could bind a large variety of receptors with high affinity, giving a wide spectrum of biological properties. 46 For example, cyclo(His−Pro) was described to exert multiple biological activities in the central nervous system, suggesting its possible application in the therapy of chronic, age-related, and neurological diseases.…”

Prebiotic Chemistry: The Role of Trimetaphosphate in Prebiotic Chemical Evolution

“…Additionally, similar to some of the conditions outlined previously, P 3 m can facilitate or accelerate the production of prebiotic-derived peptides. We have discovered that P 3 m could also act as a catalyst for the synthesis of cyclic dipeptides in an aqueous solution ( Ying et al, 2018b ; Guo et al, 2021 ). In addition to the parameters outlined above, there may be a broader range of circumstances for the synthesis of prebiotic peptides in the primordial Earth environment, but we are unable to recreate the prebiotic period’s environment to undertake relevant investigations.…”

Self-Assembly of Phenylalanine-Leucine, Leucine-Phenylalanine, and Cyclo(-leucine-phenylalanine) Dipeptides through Simulations and Experiments

“…Moreover, a lot of cyclic-peptides constitute excellent gelators, with a lot of comparisons focusing on various cyclic dipeptides including Cyclo­(-Leu-Phe) , in different solvents. Marchesan and colleagues have performed extensive studies on the gelation capacities between stereoisomers, structural isomers, and linear and cyclic dipeptides. , Furthermore, diketopiperazines and various other cyclic dipeptides act as chiral catalysts or precursors in prebiotic processes, they have cancer targeting applications when compared to linear ones, and they are considered as valuable minimal models for explaining the origins of life. Thus, a lot of comparisons are being performed, both experimental and theoretical and through combined experimental and computational studies among different kinds of cyclic peptides and the different capacities of their various morphologies, with entire libraries being dedicated to them …”