Cyclic dipeptides: Biological activities and self‐assembled materials

2020 ◽  
Author(s):  
Kaili Zhao ◽  
Ruirui Xing ◽  
Xuehai Yan
Keyword(s):  
Biological Activities ◽  
Cyclic Dipeptides ◽  
Self Assembled

scholarly journals Diketopiperazine Gels: New Horizons from the Self-Assembly of Cyclic Dipeptides

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3376
Author(s):  
Marco Scarel ◽  
Silvia Marchesan
Keyword(s):  
Drug Discovery ◽  
Enzymatic Hydrolysis ◽  
Self Assembly ◽  
Biological Activities ◽  
Functional Materials ◽  
The Self ◽  
Cyclic Dipeptides ◽  
New Horizons ◽  
Concise Review

Cyclodipeptides (CDPs) or 2,5-diketopiperazines (DKPs) can exert a variety of biological activities and display pronounced resistance against enzymatic hydrolysis as well as a propensity towards self-assembly into gels, relative to the linear-dipeptide counterparts. They have attracted great interest in a variety of fields spanning from functional materials to drug discovery. This concise review will analyze the latest advancements in their synthesis, self-assembly into gels, and their more innovative applications.

scholarly journals Macrochirality of Self-Assembled and Co-assembled Supramolecular Structures of a Pair of Enantiomeric Peptides

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhen Guo ◽  
Yongshun Song ◽  
Yujiao Wang ◽  
Tingyuan Tan ◽  
Yuwen Ji ◽  
...  
Keyword(s):  
Amino Acids ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Md Simulations ◽  
Supramolecular Structures ◽  
Molecular Chirality ◽  
Left Handed ◽  
Self Assembled ◽  
Shed Light ◽  
Good Agreement

Although macrochirality of peptides’ supramolecular structures has been found to play important roles in biological activities, how macrochirality is determined by the molecular chirality of the constituted amino acids is still unclear. Here, two chiral peptides, Ac-LKLHLHLQLKLLLVLFLFLALK-NH2 (KK-11) and Ac-DKDHDHDQDKDL DVDFDFDADK-NH2 (KKd-11), which were composed entirely of either L- or D-amino acids, were designed for studying the chiral characteristics of the supramolecular microstructures. It was found that monocomponent KK-11 or KKd-11 self-assembled into right- or left-handed helical nanofibrils, respectively. However, when they co-assembled with concentration ratios varied from 1:9 to 9:1, achiral nanowire-like structures were formed. Both circular dichroism and Fourier transform infrared spectra indicated that the secondary structures changed when the peptides co-assembled. MD simulations indicated that KK-11 or KKd-11 exhibited a strong propensity to self-assemble into right-handed or left-handed nanofibrils, respectively. However, when KK-11 and KKd-11 were both presented in a solution, they had a higher probability to co-assemble instead of self-sort. MD simulations indicated that, in their mixtures, they formed nanowires without handedness feature, a good agreement with experimental observation. Our results shed light on the molecular mechanisms of the macrochirality of peptide supramolecular microstructures.

scholarly journals Determination of 2,5-Diketopiperazines Iin Greek Processed Olives by Liquid Chromatography/Mass Spectrometry Analysis

2016 ◽  
Vol 4 (Special-Issue-October) ◽  
pp. 63-76
Author(s):  
Sotirios Bratakos ◽  
Panagiotis Zoumpoulakis ◽  
Eleni Siapi ◽  
Kyriakos Riganakos ◽  
Vassilia Sinanoglou
Keyword(s):  
Bitter Taste ◽  
Heterocyclic System ◽  
Biological Activities ◽  
Mass Spectrometry Analysis ◽  
Fermented Foods ◽  
Fragmentation Pattern ◽  
Liquid Chromatography Mass Spectrometry ◽  
Cyclic Dipeptides ◽  
Spectrometry Analysis

Diketopiperazines (DKPs) are cyclic dipeptides which have been detected in a variety of natural products, especially in thermally treated or fermented foods and beverages, providing a metallic bitter taste. DKPs, mainly due to their characteristic heterocyclic system, have been reported to exhibit a broad spectrum of biological activities including antimicrobial, antiviral, antitumor, antihyperglycaemic and antimutagenic. In the present study, several DKPs were identified in seven different Greek varieties of processed olives using HR-LC-MSn. The identification of DKPs in olive samples was achieved by comparison of their retention time and fragmentation pattern with reference DKP standards. The MSn spectra were identical to confirm the presence of specific compounds because their results associate both fragmentation pattern and fragments’ intensity. Nine compounds were found out of a total of 19 standard DKPs. The most prominent diketopiperazine was the cyclo(Phe-Phe) followed by and cyclo(Phe-Pro). Varieties where most DKPs were identified were Kothreiki, Kalamon, Throumpoelies and Helidoni.

scholarly journals Synthesis of tryptophan-containing 2,5-diketopiperazines via sequential C–H activation: total syntheses of tryprostatin A, maremycins A and B

2021 ◽  
Vol 12 (39) ◽  
pp. 13137-13143
Author(s):  
Xue-Song Yin ◽  
Wei-Yi Qi ◽  
Bing-Feng Shi
Keyword(s):  
Biological Activities ◽  
Cyclic Dipeptides ◽  
Total Syntheses ◽  
Important Type

Indole 2,5-diketopiperazines (DKPs) are an important type of metabolic cyclic dipeptides containing a tryptophan (Trp) unit possessing a range of interesting biological activities.

Mechanochemical preparation of chrysomycin A self-micelle solid dispersion with improved solubility and enhanced oral bioavailability

2021 ◽  
Author(s):  
Zhuomin Xu ◽  
Shanshan Zheng ◽  
Yulu Hong ◽  
Yue Cai ◽  
Qiuqin Zhang ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Oral Bioavailability ◽  
Biological Activities ◽  
Low Cost ◽  
Polarized Light ◽  
Average Diameter ◽  
Future Application ◽  
Amorphous Solid Dispersion ◽  
Self Assembled

Abstract Background: Chrysomycin A (CA) has been reported as numerous excellent biological activities, such as antineoplastic and antibacterial. Though, poor solubility of CA limited its application in medical field. Due to good amphiphilicity and potential anticancer effect of disodium glycyrrhizin (Na2GA) as an excipient, an amorphous solid dispersion (Na2GA/CA-BM) consisting of CA and Na2GA was prepared in the present study by mechanochemical technology (roll mill ML-007, zirconium balls, 30 rpm, 2.5 h) to improve the solubility and oral bioavailability of CA. Then, Na2GA/CA-BM was self-assembled to micelles in water. The interaction of CA and Na2GA in solid state were investigated by X-ray diffraction studies, polarized light microscopy, and scanning electron microscope. Meanwhile, the properties of the sample solution were analyzed by dynamic light scattering and transmission electron. Furthermore, the oral bioavailability and antitumor ability of Na2GA/CA-BM in vivo were tested, providing a theoretical basis for future application of CA on cancer therapy.Results: CA encapsulated by Na2GA was self-assembled to nano-micelles in water. The average diameter of nano-micelle was 131.6 nm, and zeta potential was -11.7 mV. Three physicochemical detections showed that CA was transformed from crystal into amorphous form after treated with ball milling and the solubility increased by 50 times. Na2GA/CA-BM showed a significant increase of the bioavailability about 2 time that of free CA. Compared with free CA, the in-vivo antitumor studies also exhibited that Na2GA/CA-BM had an excellent inhibition of tumor growth.Conclusions: Na2GA/CA-BM nanoparticles (131.6 nm, -11.7 mV) prepared by simple and low-cost mechanochemical technology can improve oral bioavailability and antitumor efficacy of CA in vivo, suggesting a potential formulation for efficient anticancer treatment.

A Minimalistic Hydrolase Based on Co-Assembled Cyclic Dipeptides

2019 ◽  
Author(s):  
Alexander Kleinsmann ◽  
Boris Nachtsheim
Keyword(s):  
Cyclic Dipeptides ◽  
Self Assembled ◽  
Primordial Earth

This paper describes minimalistic cyclic dipeptides acting as esterase-mimicks in a self-assembled hydrogel state. It demonstrates that cyclic dipeptides could have acted as enzyme-precursors on a primordial earth and hence be important for abiogenesis. <br>

Quantum-Chemical ab initio Study of Side Chain pKa of Linear and Cyclic Lysine Dipeptides

2020 ◽  
pp. 1-9
Author(s):  
Mohsen Sargolzaei ◽  
Hossein Nikoofard ◽  
Majid Namayandeh Jorabchi
Keyword(s):  
Experimental Data ◽  
Hydrogen Bond ◽  
Ab Initio ◽  
Quantum Chemical ◽  
Biological Activities ◽  
Side Chain ◽  
Ab Initio Study ◽  
Cyclic Dipeptides ◽  
Pka Values ◽  
Pka Value

Cyclic dipeptides show interesting biological activities such as antitumor, antiviral and so on. In biological systems, the bioavailability of drugs is determined by several parameters such as pKa values. In this study, we used DFT and thermodynamics cycle to determine pKa value of side chain of lysine in linear and cyclic dipeptides. All considered dipeptides were optimized using B3LYP and RMSD tool was used to compare the optimized structures. The calculated pKa values were compared with the available experimental data. Our results show that pKa of side chain of lysine increases for cyclic dipeptides compared to the linear ones. To justify the reason of increasing of pKa of cyclic dipeptides, we used NBO and AIM analyses. The analyses showed that a hydrogen bond in cyclic lysine dipeptides is responsible for increasing of pKa.

scholarly journals Structural-based engineering expands the substrate scope of a cyclodipeptide synthase

2021 ◽  
Author(s):  
Emmajay Sutherland ◽  
Christopher Harding ◽  
Clarissa Czekster
Keyword(s):  
Crystal Structure ◽  
Amino Acids ◽  
Biological Activities ◽  
Substrate Selectivity ◽  
Cyclic Dipeptides ◽  
Successive Generations ◽  
The Way

Cyclodipeptide synthases (CDPSs) are a growing family of enzymes capable of producing a large variety of cyclodipetide products using aminoacylated tRNA. Histidine-containing cyclic dipeptides have important biological activities as anticancer and neuroprotective molecules. Out of the 120 experimentally validated CDPS members, only two are known to accept histidine as a substrate. Here, we studied the activities of both Para-CDPS from Parabacteroides sp. 20_3 and Parcu-CDPS from Parcubacteria bacterium RAAC4_OD1_1 which synthesise cyclo(His-Phe) and cyclo(His-Pro) respectively. Both enzymes accepted canonical and non-canonical amino acids as substrates to generate a library of novel molecules. In order to understand the substrate selectivity of these CDPSs, the crystal structure of Parcu-CDPS was solved (alongside a number of mutants) and the role of residues important for catalysis and histidine recognition were probed using mutagenesis. Three successive generations of mutants containing both single and double residue substitutions were generated leading to a change in substrate selectivity from histidine to phenylalanine and leucine. The research detailed herein is the first instance of successful engineering of a CDPS to yield different products, paving the way to direct the promiscuity of these enzymes to produce molecules of our choosing.

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