Cyclic Dipeptides Research Articles

Anticorrosive waterborne polyurethane coatings derived from castor oil and renewable diols

Although vegetable oil-based waterborne polyurethane (WPUs) possesses unique advantage like environmental friendliness, the shortcomings of low mechanical properties havehampered its practical implementations. In this work, sustainable diols, isosorbide (IS) and L-tyrosine derived cyclic dipeptide (L-CD), were employed into the anionic castor oil based WPU backbones via a molecular design strategy respectively (denoted as WPU-A and WPU-B). Their impact on the stability of the dispersion as well as the performance of casting films were investigated thoroughly. Result shown that the tensile strength of the films reached up to 29.56 MPa, while the toughness remained at 20.12 MJ/m−3, outperforming the state-of-art castor oil-based WPU systems. Specifically, WPU-B films exhibited superior performance than WPU-A ones possessing the similar hard segment contents, which presumably attribute to a higher density of hydrogen bonds within the network. The glass transition temperature (Tg) of WPUs were tailored in the range of 5.93 °C to 57.23 °C, and the highest value was prominent in the reported systems. Interestingly, the incorporation of sustainable diols into WPUs improved the anticorrosion performance towards 45# steel, which stemmed from the robust, hydrophobic properties of the WPU films. This study offered strategies for tailoring the physical properties of environmental benign WPUs and paved the ways towards developing high performance coatings for anticorrosion applications.

Baoshanmycin and a New Furanone Derivative from a Soil-Derived Actinomycete, Amycolatopsis sp. YNNP 00208.

Actinomycetes have being regarded as a treasure reservoir of various bioactive secondary metabolites and devoted many antibiotics in clinicals. Amycolatopsis sp. YNNP 00208 was isolated from a soil sample collected in Gaoligong Mountain area, Yunnan Province, China. Chemical investigation of its fermentation broth led to a new amide, baoshanmycin (1), and a new furanone derivative, 3-(1,3-dihydroxybutyl)-4-methylfuran-2(H)-one (2), together with eight known compounds, including two amides (3-4), four cyclic dipeptides (5-8), and two deoxyribonucleosides (9-10). Their structures were established on basis of the 1D- and 2D-NMR spectroscopic data, along with the HR-ESI-MS experiments. Baoshanmycin (1) showed moderate antimicrobial activities against Candida albicans, and weak activities against Staphylococcus aureus, multi-drug resistant Staphylococcus aureus, Bacillus subtilis, Listeria monocytogenes, fluconazole-resistant Candida albicans. Baoshanmycin (1) presented strong antioxidant activity and moderate anti-acetylcholinesterase activity. The other compound 3-(1,3-dihydroxybutyl)-4-methylfuran-2(H)-one (2) and the known compounds (3-10) showed moderate antioxidant activity.

How Symmetry Influences the Dissociation of Protonated Cyclic Peptides

Protonated cyclic dipeptides undergo collision-induced dissociation, and this reaction mechanism strongly depends on the symmetry and the nature of the residues. We review the main dissociation mechanism for a series of cyclic dipeptides, obtained through chemical dynamics simulations. The systems range from the symmetrical cyclo-(glycyl-glycyl), with two possible symmetrical protonation sites located on the peptide ring, to cyclo-(tyrosyl-prolyl), where the symmetry of protonation sites on the peptide ring is broken by the dissimilar nature of the different residues. Finally, cyclo-(phenylalanyl-histidyl) shows a completely asymmetric situation, with the proton located on one of the dipeptide side chains, which explains the peculiar fragmentation mechanism induced by shuttling the proton, whose efficiency is strongly dependent on the relative chirality of the residues.

Limosilactobacillus (Lactobacillus) fermentum ALAL020, a Probiotic Candidate Bacterium, Produces a Cyclic Dipeptide That Suppresses the Periodontal Pathogens Porphyromonas gingivalis and Prevotella intermedia

Periodontal disease develops as a result of oral microbiota in dysbiosis, followed by the growth of periodontal pathogens such as Porphyromonas gingivalis and Prevotella intermedia. In case of acute symptoms, antibacterial agents and disinfectants are administered, however the appearance of drug-resistant bacteria and allergies cause problems. In recent years, studies on the effects of probiotics have been conducted as an alternative therapy for periodontitis. However, the basic mechanism of the inhibitory effect of probiotic bacteria on periodontal disease has not been clearly elucidated. To clarify the antibacterial mechanism of probiotics against periodontal pathogens, we used Limosilactobacillus (Lactobacillus) fermentum ALAL020, which showed the strongest antibacterial activity against P. gingivalis and P. intermedia among 50 screened lactic acid bacteria strains. The antibacterial substances produced were identified and structurally analyzed. After neutralizing the MRS liquid culture supernatant of ALAL020 strain, the molecular weight (m/z) of the main antibacterial substance separated by gel filtration column chromatography and reverse phase HPLC was 226.131. This low molecular weight compound was analyzed by LC-MS and disclosed the composition formula C11H18O3N2, however the molecular structure remained unknown. Then, structural analysis by NMR revealed C11H18O3N2 as the cyclic dipeptide, “hexahydro-7-hydroxy-3- (2-methylpropyl) pyrrolo [1,2-a] pyrazine-1,4-dion cyclo (Hyp-Leu) “. Based on the results of this analysis, cyclo (Hyp-Leu) was chemically synthesized and the antibacterial activity against P. gingivalis and P. intermedia was measured. The minimum inhibitory concentration (MIC) was 2.5 g/L and the minimum bactericidal concentration (MBC) was shown to be less than 5 g/L. In addition, an in vitro epithelial tissue irritation test at 10 g/L showed no tissue toxicity. So far there are no reports of this peptide being produced by probiotic bacteria. Furthermore, antibacterial activity of this cyclic dipeptide against periodontal disease bacteria has not been confirmed. The results of this study might lead to a comprehensive understanding of the antibacterial mechanism against periodontal disease bacteria in future, and are considered applicable for the prevention of periodontal disease.

Novel glyproline GZK-111 with neuropsychotropic activity

Thе article represents a review of our own researches, which describes the design, synthesis and pharmacological properties of linear substituted glyproline GZK-111, a potential drug for the complex treatment of psychiatric pathologies, including anxiety, depressive disorders, and cognitive impairment. The relationship between structure and activity in a series of this glyproline analogs is described. The experimental evidence of the GZK-111 ability to metabolized with the formation of cycloprolylglycine, which is identical to the endogenous cyclic dipeptide, is presented. The data on toxicological and pharmacokinetic studies of GZK-111 are presented.

Polyols Induce the Production of Antifungal Compounds by Lactobacillus plantarum.

Mycotoxins may be present in nuts, coffee, cereals, and grapes, among other products. Increasing concerns about human health and environmental protection have driven the application of biological control techniques that can inhibit fungal contaminants. In this study, the growth inhibition of the ochratoxigenic fungus Aspergillus carbonarius Ac 162 was evaluated using 5 lactic acid bacteria (LAB). The LAB studied were Lactobacillus plantarum MZ801739 (J), Lactobacillus plantarum MZ809351 (31) and Lactobacillus plantarum MZ809350 (34), isolated in the Ivory Coast, and Lactobacillus plantarum MN982928 (3) and Leuconostoc citreum MZ801735 (23), isolated in Mexico. J, 31, 34, 3 and 23 are the internal strain codes from our laboratory. LAB were cultivated in De Man, Rogosa and Sharpe (MRS) broth, and different polyols (glycerol, mannitol, sorbitol, and xylitol) were added to the culture broth to stimulate the production of antifungal compounds. The fungal inhibition studies were performed using the poisoned food technique. The highest inhibition of A. carbonarius growth was obtained by cultivating L. plantarum MZ809351 in the presence of xylitol and glycerol. Under these conditions, 1 L of the L. plantarum MZ809351 cultures were used to identify antifungal compounds. The compounds were concentrated by solid-phase extraction and then characterized by GC-MS. In addition to 9-octadecenoic acid, 3 diketopiperazines or cyclic dipeptides were identified, including cyclo (Leu-Leu), cyclo (Pro-Gly) and cyclo (Val-Phe), which were compounds related to microbial antifungal activities. Xylitol and glycerol induced the production of these antifungal compounds against A. carbonarius Ac 162. On the other hand, adding xylitol and glycerol to the MRS broth reduced the Ochratoxin A (OTA) content to 56.8 and 54.7%, respectively. This study shows the potential for using L. plantarum MZ809351 as a biocontrol agent to prevent the growth of A. carbonarius and reduce the production of OTA in foods.

Selection of Amino Acid Chirality Induced by Cyclic Dipeptide Synthesis in Plausible Prebiotic Conditions

The biological system uses L-amino acids (L-AAs) to construct peptides. The selection of AA chirality in the prebiotic Earth still remains a mystery. Here we report the intrinsic mechanism of AA chiral selection in the formation of prebiotic proline-containing cyclic dipeptide (DKPs). The DKPs were synthesized by equal amounts of L-AA and D-AA with L-Pro that exhibited a clear preference for D-AA as opposed to L-AA. And surprisingly, the L-AA was preferred over D-AA in the mirror-image system with D-Pro. These results indicate that prebiotic DKPs synthesis has a certain selectivity for AA chirality preceded the biological enzymatic catalysis.

S-Benzyl cysteine based cyclic dipeptide super hydrogelator: Enhancing efficacy of an anticancer drug via sustainable release.

Peptide-based low molecular weight supramolecular hydrogels hold promising aspects in various fields of application especially in biomaterial and biomedical sciences such as drug delivery, wound healing, tissue engineering, cell proliferation, and so on due to their extreme biocompatibility. Unlike linear peptides, cyclic peptides have more structural rigidity and tolerance to enzymatic degradation and high environmental stability which make them even better candidates for the above-said applications. Herein, a new small cyclic dipeptide (CDP) cyclo-(Leu-S-Bzl-Cys) (P1) consisting of L-leucine and S-benzyl protected L-cysteine was reported which formed a hydrogel at physiological conditions (at 37°C and pH = 7.46). The hydrogel formed from the cyclic dipeptide P1 showed very good tolerance towards environmental parameters such as pH and temperature and was seen to be stable for more than a year without any deformation. The hydrogel was thermoreversible and stable in the pH range 6-12. Mechanical strength of P1 hydrogel was measured by rheology experiments. Atomic force microscopy (AFM) and field emission scanning electron microscopy (FE-SEM) images revealed that, in aqueous solvents, P1 self-assembled into a highly cross-linked nanofibrillar network which immobilized water molecules inside the cages and formed the hydrogel. The self-assembled cyclic dipeptide acquired the antiparallel β-sheet secondary structure, which was evident from CD and Fourier transform infrared (FT-IR) studies. The β-sheet arrangement and formation of amyloid fibrils were further established by ThT binding assay. Furthermore, P1 was able to form a hydrogel in the presence of the anticancer drug 5-fluorouracil (5FU), and sustainable release of the drug from the hydrogel was measured in vitro. The hydrogelator P1 showed almost no cytotoxicity towards the human colorectal cancer cell line HCT116 up to a considerably high concentration and showed potential application in sustainable drug delivery. The co-assembly of 5FU and P1 hydrogel exhibited much better anticancer activity towards the HCT116 cancer cell line than 5FU alone and decreased the IC50 dose of 5FU to a much lower value.

Bio‐basedbenzoxazine from renewableL‐tyrosine: Synthesis, polymerization, and properties

AbstractDeveloping thermosets derived from renewable sources is of great importance. In this work, a fully bio‐based benzoxazine monomer, 3,6‐bis((3‐(furan‐2‐ylmethyl)‐3,4‐dihydro‐2H‐benzo[e][1,3]oxazin‐6‐yl)methyl)piperazine‐2,5‐dione (TCDPF), is conveniently synthesized from L‐tyrosine cyclic dipeptide (TCDP), furfurylamine and paraformaldehyde. The chemical structure of TCDPF is confirmed by nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy (FT‐IR) techniques. The curing behavior of TCDPF is investigated by differential scanning calorimetry and in situ FT‐IR techniques. After temperature‐programmed curing, the thermomechanical property and thermal stability of the resulting TCDPF polymer (PTCDPF) are evaluated by dynamic mechanical analysis and thermogravimetric analysis techniques, respectively. It is found that PTCDPF have excellent comprehensive performance such as high glass transition temperature (Tg = 322 °C), high thermal degradation temperature (T5% = 342 °C,T10% = 395 °C in N2atmosphere), and high char yield (CY = 51.3% at 800 °C in N2atmosphere). The results demonstrate that L‐tyrosine is a promising bio‐based raw material for preparing high performance polybenzoxazines.

Anti-Quorum-Sensing Activity of Tryptophan-Containing Cyclic Dipeptides.

Quorum sensing (QS) can regulate the pathogenicity of bacteria and the production of some virulence factors. It is a promising target for screening to find anti-virulence agents in the coming post-antibiotics era. Cyclo (L-Trp-L-Ser), one variety of cyclic dipeptides (CDPs), isolated from a marine bacterium Rheinheimera aquimaris, exhibited anti-QS activity against Chromobacterium violaceum CV026 and Pseudomonas aeruginosa PAO1. Unlike the CDPs composed of phenylalanine or tyrosine, the anti-QS activity has been widely studied; however, cyclo (L-Trp-L-Ser) and derivatives, containing one tryptophan unit and one non-aromatic amino acid, have not been systematically explored. Herein, the cyclo (L-Trp-L-Ser) and seven derivatives were synthesized and evaluated. All tryptophane-contained CDPs were able to decrease the production of violacein in C. violaceum CV026 and predicted as binding within the same pocket of receptor protein CviR, but in lower binding energy compared with the natural ligand C6HSL. As for P. aeruginosa PAO1, owning more complicated QS systems, these CDPs also exhibited inhibitory effects on pyocyanin production, swimming motility, biofilm formation, and adhesion. These investigations suggested a promising way to keep the tryptophan untouched and make modifications on the non-aromatic unit to increase the anti-QS activity and decrease the cytotoxicity, thus developing a novel CDP-based anti-virulence agent.

Mass Spectrometric Fingerprints of Bacteria and Archaea for Life Detection on Icy Moons.

The icy moons of the outer Solar System display evidence of subsurface liquid water and, therefore, potential habitability for life. Flybys of Saturn's moon Enceladus by the Cassini spacecraft have provided measurements of material from plumes that suggest hydrothermal activity and the presence of organic matter. Jupiter's moon Europa may have similar plumes and is the target for the forthcoming Europa Clipper mission that carries a high mass resolution and high sensitivity mass spectrometer, called the MAss Spectrometer for Planetary EXploration (MASPEX), with the capability for providing detailed characterization of any organic materials encountered. We have performed a series of experiments using pyrolysis-gas chromatography-mass spectrometry to characterize the mass spectrometric fingerprints of microbial life. A range of extremophile Archaea and Bacteria have been analyzed and the laboratory data converted to MASPEX-type signals. Molecular characteristics of protein, carbohydrate, and lipid structures were detected, and the characteristic fragmentation patterns corresponding to these different biological structures were identified. Protein pyrolysis fragments included phenols, nitrogen heterocycles, and cyclic dipeptides. Oxygen heterocycles, such as furans, were detected from carbohydrates. Our data reveal how mass spectrometry on Europa Clipper can aid in the identification of the presence of life, by looking for characteristic bacterial fingerprints that are similar to those from simple Earthly organisms.

The inhibitory effect of Periplaneta americana L. on hepatocellular carcinoma: Explore the anti-hepatocellular carcinoma active site and its mechanism of action

Ethnopharmacological relevanceThe American cockroach (Periplaneta americana L.) belongs to the family Blattidae, order Blattodea, and class Insecta. Its medicinal history in China spans thousands of years. In recent years, the anti-tumour activity of American cockroach has gradually attracted the attention of researchers and has a good application prospect in the treatment of tumours. Periplaneta americana has been found to contain proteins, peptides, amino acids and nucleosides. Pharmacological studies have shown that P. americana has anti-tumour, tissue repair, immunoregulatory and other activities. In this study, we investigated the chemical composition and mechanism of action of its active site against hepatocellular carcinoma. Materials and methodsWe adopted ultra-performance liquid chromatography quadrupole Orbitrap high-resolution mass spectrometry (UPLC–Q-Orbitrap HRMS), measuring the accurate relative molecular mass, fragment ion peak, chromatographic retention time and reference substance information of the compound obtained by HRMS, to identify the chemical components of the anti-hepatocellular carcinoma (HCC) active site of P. americana based on data from relevant literature. We used western blotting (WB) to detect the expression levels of phosphoinositide 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt) and Akt in the PI3K/Akt pathway and further study the molecular mechanism of the active site of P. americana against HCC. ResultsUPLC–Q-Orbitrap HRMS identified 35 compounds from the active site of P. americana. Of these, 10 were amino acids, 1 was an alkaloid, 6 were nucleosides and their bases, 4 were dipeptides and cyclic dipeptides, 8 were organic acids, 2 were isoflavones and 4 were other compounds; 8 of these compounds were confirmed by comparison with the reference substance. The WB results showed that the relative expression levels of PI3K and p-Akt protein in the active site of P. americana in the medium-dose (concentration, 0.15624 mg⋅mL−1) and high-dose (concentration, 0.31250 mg⋅mL−1) experimental groups were significantly reduced compared with the blank control group (P < 0.05 or P < 0.01), whereas the expression level of Akt protein did not significantly change amongst the groups (P > 0.05). ConclusionThis study found that the anti-HCC active site of P. americana is composed of multiple components that can reduce the relative expression of PI3K and p-Akt protein. It exerts its anti-HCC effect by regulating the PI3K/Akt pathway.

Differential copper-guided architectures of amyloid β peptidomimetics modulate oxidation states and catalysis.

Orchestration of differential architectures of designer peptidomimetics that modulate metal oxidation states to perform multiple chemical transformations remains a challenge. Cu-chelation and self-assembly properties of amyloid β (Aβ14-23) peptide were tuned by the incorporation of cyclic dipeptide (CDP) and pyrene (Py) as the assembly directing and reporting units, respectively. We explore the molecular architectonics of Aβ14-23 derived peptidomimetics (AkdNMCPy) to form differential architectures that stabilize distinct Cu oxidation states. The fibrillar self-assembly of AkdNMCPy is modulated to form nanosheets by the one-off addition of CuII. Notably, the serial addition of CuII resulted in the formation of micelle-like core–shell architectures. The micelle-like and nanosheet architectures were found to differentially stabilize CuII and CuI states and catalyze tandem oxidative-hydrolysis and alkyne–azide cycloaddition reactions, respectively.

Antifungal activity of lactic acid bacteria and their application in food biopreservation.

Lactic acid bacteria (LAB) are ubiquitous bacteria associated with spontaneous lactic fermentation of vegetables, dairy and meat products. They are generally recognized as safe (GRAS), and they are involved in transformation of probiotic lacto-fermented foods, highly desired for their nutraceutical properties. The antifungal activity is one of the exciting properties of LAB, because of its possible application in food bio-preservation, as alternative to chemical preservatives. Many recent research works have been developed on antifungal activity of LAB, and they demonstrate their capacity to produce various antifungal compounds, (i.e. organic acids, PLA, proteinaceous compounds, peptides, cyclic dipeptides, fatty acids, and other compounds), of different properties (hydrophilic, hydrophobic and amphiphilic). The effectiveness of LAB in controlling spoilage and pathogenic fungi, demonstrated in different agricultural and food products, can be due to the synergistic effect between their antifungal compounds of different properties; where the amphiphilic-compounds allow the contact between the target microbial cell (hydrophilic compartment) and antifungal hydrophobic-compounds. Further studies on the interaction between compounds of these three properties are to de be developed, in order to highlight more their mechanism of action, and make LAB more profitable in improving shelf life and nutraceutical properties of foods.

Reversible photodissipation of composite photochromic azobenzene-alginate supramolecular hydrogels.

Supramolecular smart materials can quickly elicit macroscopic changes upon external stimulation. Here we report that an azobenzene-containing cyclic dipeptide can form composite supramolecular hydrogels with alginate based on the charge complementarity, at lower loading than the critical gelation concentrations of either component. The gels can reversibly dissipate to fluids with UV light. They can also encapsulate and photorelease fluorescent cargo. Upon treatment of the gels with aqueous calcium salts, the alginate component is permanently cross-linked and the photochromic component is solubilized.

Hydrothermal, Catalyst-Free Production of a Cyclic Dipeptide from Lysine

Hydrothermal, Catalyst-Free Production of a Cyclic Dipeptide from Lysine

How change in chirality prevents β-amyloid type interaction in a protonated cyclic dipeptide dimer.

The protonated dimers of the diketopiperazine dipeptide cyclo (LPhe-LHis) and cyclo (LPhe-DHis) are studied by laser spectroscopy combined with mass spectrometry to shed light on the influence of stereochemistry on the clustering propensity of cyclic dipeptides. The marked spectroscopic differences experimentally observed in the hydride stretch region are well accounted for by the results of DFT calculations. Both diastereomeric protonated dimers involve a strong ionic hydrogen bond from the protonated imidazole ring of one monomer to the neutral imidazole nitrogen of the other. While this strong interaction is accompanied by a single NH⋯O hydrogen bond between the amide functions of the two moieties for the protonated dimer of cyclo (LPhe-DHis), that of cyclo (LPhe-LHis) involves two NH⋯O interactions, forming the motif of an antiparallel β sheet. Therefore, a change in chirality of the residue prevents the formation of the β sheet pattern observed in the amyloid type aggregation. These results emphasize the peculiar role of the histidine residue in peptide structure and interaction.

Cyclo(Val-Pro) and Cyclo(Leu-Hydroxy-Pro) from Pseudomonas sp. (ABS-36) alleviates acute and chronic renal injury under in vitro and in vivo models (Ischemic reperfusion and unilateral ureter obstruction)

The study aimed to identify small molecules having potentiality in alleviating renal injury. Two natural compounds cyclo(Val-Pro) (1) and cyclo(Leu-Hydroxy-Pro) (2) were first evaluated under acute renal injury model of ischemic reperfusion at different doses of 25, 50 and 75 mg/kg body weight. Further, the compounds were subjected to antimycin A-induced ischemic in vitro study (NRK-52E cell lines). Both the compounds significantly decreased plasma IL-1β levels (P < 0.05). Also, the mRNA expression levels of inflammatory markers (TNF-α, IL-6 and IL-1β) and renal injury markers (KIM-1, NGAL, α-GST and π-GST) in the renal tissues were significantly alleviated (P < 0.01) along with the improvement in histological damage and control over neutrophil infiltration as a result of ischemic reperfusion. The in vitro study revealed the protective effect against antimycin A-induced cytotoxicity (P < 0.05) and antiapoptotic effect acting through the regulation of Bax, caspase 3 (pro and cleaved) and BCL2 with reduction in Annexin+PI+ cells. Further, the compound cyclo(Val-Pro) (1) was evaluated (50 mg/kg body weight dose) in chronic unilateral ureter obstruction model of renal injury in mice and TGF-β-induced in vitro fibrotic model (NRK-49F cell lines). Cyclo(Val-Pro) (1) significantly reduced the expression levels of fibrotic markers (collagen-1, α-SMA and TGF-β) and showed marked alleviation of renal fibrosis (sirius red staining). Also, the proliferation of TGF-β-induced NRK-49F cells was significantly reduced along with decreased levels of collagen-1 and α-SMA in immunohistochemistry studies. In conclusion, the compounds significantly abrogated ischemic injury by inhibiting renal inflammation and tubular epithelial apoptosis. Further, cyclo (Val-Pro) (1) exhibited significant anti-fibrotic activity through the inhibition of fibroblast activation and proliferation. Thus, these proline-based cyclic dipeptides are recommended as drug leads for treating renal injury.

Lentzeacins A-E, New Bacterial-Derived 2,5- and 2,6-Disubstituted Pyrazines from a BGC-Rich Soil Bacterium Lentzea sp. GA3-008.

Pyrazines (1,4-diazirines) are an important group of natural products that have tremendous monetary value in the food and fragrance industries and can exhibit a wide range of biological effects including antineoplastic, antidiabetic and antibiotic activities. As part of a project investigating the secondary metabolites present in understudied and chemically rich Actinomycetes, we isolated a series of six pyrazines from a soil-derived Lentzea sp. GA3-008, four of which are new. Here we describe the structures of lentzeacins A-E (1, 3, 5 and 6) along with two known analogues (2 and 4) and the porphyrin zincphyrin. The structures were determined by NMR spectroscopy and HR-ESI-MS. The suite of compounds present in Lentzea sp. includes 2,5-disubstituted pyrazines (compounds 2, 4, and 6) together with the new 2,6-disubstituted isomers (compounds 1, 3 and 5), a chemical class that is uncommon. We used long-read Nanopore sequencing to assemble a draft genome sequence of Lentzea sp. which revealed the presence of 40 biosynthetic gene clusters. Analysis of classical di-modular and single module non-ribosomal peptide synthase genes, and cyclic dipeptide synthases narrows down the possibilities for the biosynthesis of the pyrazines present in this strain.

Stackable Aromatic Dipeptide Ring Structures toward Nanotube Formation: Thermodynamics and Interactions in Gas‐Phase and Solution

AbstractIncreasing attention has been drawn towards self‐assembling dipeptide nanotube materials (NT) for their tunable properties. Despite recent advances, a fundamental understanding of the conditions that drive the self‐assembly process is still lacking. Here, we report the structures, thermodynamics, and underlying interactions of the nanotube forming potential of cyclic and linear aromatic dipeptides phenylalanine‐tyrosine, tryptophan‐tyrosine, and dityrosine via the piecewise self‐assembly mechanism. The cyclic dipeptides have better favorability of oligomerization in the gas phase than the linear dipeptides, largely due to the enthalpic gain of forming more hydrogen bonds, suggesting that the piecewise mechanism is plausible for vapor deposition methods. Oligomerization in solution, which would require desolvation of free monomers, was shown to be thermodynamically unfavorable, especially in polar solvents, demonstrating the need for an external stimulus for the crystallization of NTs. The generated oligomeric rings show structural robustness and symmetry, allowing excellent stacking potential in both lateral and axial directions. The nature of the sidechains significantly affects the stabilizations within the oligomeric structure. The insights generated can be used as a basis for dipeptide modifications that could enhance targeted NT properties for different applications.