- |||||||||| Ampion (diketopiperazine) / Ampio
PK/PD data, Journal: Preparation, characterization, and pharmacodynamics of insulin-loaded fumaryl diketopiperazine microparticle dry powder inhalation. (Pubmed Central) - Dec 19, 2019
Moreover, no inflammatory reaction was observed during the safety study. To sum up, the aim was to develop a non-injection system for insulin, INS@FDKP-MPs powder inhalation with high dose, low toxicity, and good lung deposition inhalation could rapidly decrease the blood glucose level without immune stimulation, which shows remarkably potential on diabetes treatment by pulmonary delivery route.
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Journal: Peptide bond conformation in peptides and proteins probed by dipolar coupling-chemical shift tensor correlation solid-state NMR. (Pubmed Central) - Nov 28, 2019
The experiments are demonstrated for model peptides glycylglycine and 2,5-diketopiperazine containing trans and cis peptide bonds, respectively. Subsequently, the measurements are extended to two representative proteins that contain exclusively trans peptide bonds, microcrystalline B3 immunoglobulin domain of protein G and Y145Stop human prion protein amyloid fibrils, to illustrate their applicability to a wide range of protein systems.
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Review, Journal: Non-lipopeptide fungi-derived peptide antibiotics developed since 2000. (Pubmed Central) - Nov 24, 2019
The 2,5-diketopiperazines (DKPs) are the smallest cyclopeptides and their basic structure includes a six-membered piperazine nucleus...To date, only cyclosporin A has been developed into a commercial product...Additionally, biosynthases of tardioxopiperazines and neoechinulins are highlighted. These compounds have attracted considerable interest within the pharmaceutical and agrochemical industries.
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Journal: Isolation and structural characterization of a non-diketopiperazine phytotoxin from a potato pathogenic Streptomyces strain. (Pubmed Central) - Nov 19, 2019
The metabolite is produced in yields of ∼200 mg/L of culture media, induces deep necrotic lesions on potato tubers, stuns root and shoot growth in radish seedlings, and is comparatively more aggressive than thaxtomin A. This is the first time that desmethylmensacarcin, a member of a class of compounds known for their antitumor and antibiotic activity, is associated with phytotoxicity. More importantly, it represents the discovery of a new virulence factor related to potato common scab, an economically-important disease affecting potato production worldwide.
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Journal: Structural basis for partition of the cyclodipeptide synthases into two subfamilies. (Pubmed Central) - Oct 4, 2019
Cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides that can be further used for the synthesis of diketopiperazines...This gives a structural basis for the partition of CDPSs into two subfamilies. Despite these differences, the catalytic residues adopt similar positioning regardless of the subfamily suggesting that the XYP and NYH motifs correspond to two structural solutions to facilitate the reactivity of the catalytic serine residue.
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Journal: Quorum sensing system-regulated genes affect the spoilage potential of Shewanella baltica. (Pubmed Central) - Oct 2, 2019
Moreover, diketopiperazine (DKP) quorum sensing (QS) signaling molecules regulated biofilm formation and spoilage gene expression, indicating a relationship between the QS system, biofilm formation and spoilage potential. Our results suggest that DKPs and spoilage genes are potential targets for developing novel food antiseptics, as well as new markers for fish product spoilage.
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Journal: Customizable Lipid Nanoparticle Materials for the Delivery of siRNAs and mRNAs. (Pubmed Central) - Oct 2, 2019
Eight lipid materials are synthesized, and 16 total formulations are screened for activity in vitro; the lead material is evaluated with mRNA for in vivo use and demonstrates luciferase protein expression in the spleen. In undertaking this approach, not only do we develop synthetic routes to delivery materials, but we also reveal structural criteria that could be useful for developing next-generation delivery materials for RNA therapeutics.
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Journal: Secondary metabolites produced by Microbacterium sp. LGMB471 with antifungal activity against the phytopathogen Phyllosticta citricarpa. (Pubmed Central) - Sep 20, 2019
Three isoflavones and five diketopiperazines were identified, and the compounds 7-O-β-D-glucosyl-genistein and 7-O-β-D-glucosyl-daidzein showed high activity against P. citricarpa, with the MIC of 33 μg/mL and inhibited the production of asexual spores of P. citricarpa on leaves and citrus fruits...Our data suggest the use of Microbacterium sp. LGMB471 or its metabolites as an ecological alternative to be used in association with the fungicides for the control of CBS disease.
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Journal: Mechanism of Permanganate-Promoted Dihydroxylation of Complex Diketopiperazines: Critical Roles of Counter-cation and Ion-Pairing. (Pubmed Central) - Sep 8, 2019
We used the developed mechanistic knowledge to rationalize an experimentally observed oxidation pattern for C-indole-substituted diketopiperazine (+)-5 under optimal oxidation conditions: namely, the formation of diol (-)-6 as a single diastereomer and lack of the ketone products. We proposed two factors that may impede the ketone formation: (i) the conformational flexibility of the diketopiperazine ring, and (ii) hindrance of this site, making it less accessible to the ion-paired oxidant species.
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Journal: New Diketopiperazines from a Marine-Derived Fungus Strain Aspergillus versicolor MF180151. (Pubmed Central) - Sep 3, 2019
Their bioactivities were evaluated against Candida albicans, Bacillus subtilis, Staphylococcus aureus, methicillin-resistant S. aureus, Pseudomonas aeruginosa, and Bacillus Calmette-Guérin. Compounds 1-4 showed no activities against the pathogens, and compounds 5 and 6 showed moderate activities against S. aureus and methicillin-resistant S. aureus.
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Journal: Versatile Synthetic Approach for Selective Diversification of Bicyclic Aza-Diketopiperazines. (Pubmed Central) - Aug 29, 2019
These scaffolds containing either azido or amino groups were obtained by a key Rh(I)-catalyzed hydroformylative cyclohydrocarbonylation reaction of allyl-substituted aza-DKP. The methodology is readily amenable to the parallel synthesis of original aza-DKPs to enlarge the chemical diversity of aza-heterocycles.
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Journal: Catalytic Asymmetric Synthesis of Diketopiperazines by Intramolecular Tsuji-Trost Allylation. (Pubmed Central) - Aug 27, 2019
We report the intramolecular Tsuji-Trost reaction of Ugi adducts to give spiro-diketopiperazines in high yield and with high enantioselectivity. This approach allows the catalytic asymmetric construction of a broad range of these medicinally important heterocycles under mild conditions, in two steps from cheap, commercially available starting materials.
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Clinical, Journal: Residual Complexity Does Impact Organic Chemistry and Drug Discovery: The Case of Rufomyazine and Rufomycin. (Pubmed Central) - Aug 21, 2019
...The new diketopiperazine, rufomyazine (6), and the previously known antibiotic, rufomycin (7), represent a prototypical case of RC that (almost) resulted in the misassignment of biological activity...The initially observed activity was eventually attributed to a very minor contamination (0.24% [m/m]) with a highly active cyclic peptide (MIC ∼ 0.02 μM), subsequently identified as an analogue of 7. This study illustrates the serious implications RC can exert on organic chemistry and drug discovery, and what efforts are vital to improve lead validation and efficiency, especially in NP-related drug discovery programs.
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Journal: Discovery and biosynthesis of the antibiotic bicyclomycin in distant bacterial classes. (Pubmed Central) - Aug 17, 2019
...BCM is structurally characterized by a core cyclo(l-Ile-l-Leu) 2,5-diketopiperazine (DKP) that is extensively oxidized...Here, we report the identification of the bicyclomycin biosynthetic gene cluster in the known producing organism, which will enable the engineered production of new bicyclomycin derivatives. The identification of this gene cluster also led to the discovery of hundreds of bicyclomycin pathways encoded in highly diverse bacteria, including the opportunistic pathogenThis wide distribution of a complex biosynthetic pathway is very unusual, and provides an insight into how a pathway for an antibiotic can be transferred between diverse bacteria.
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Journal: A Transannular Rearrangement Reaction of a Pyrroloindoline Diketopiperazine. (Pubmed Central) - Aug 16, 2019
Oxaline, glandicoline, and meleagrin contain a unique triazaspirocyclic structure. Attracted by their biological activities, we attempted a novel strategy, mimicking a proposed biosynthetic pathway for glandicoline B in Penicillium chrysogenum and Penicillium oxalicum and using a transannular rearrangement to the desired triazaspirocycle 15.
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Journal: Development and evaluation of cationic amphiphilic antimicrobial 2,5-diketopiperazines. (Pubmed Central) - Aug 8, 2019
Attracted by their biological activities, we attempted a novel strategy, mimicking a proposed biosynthetic pathway for glandicoline B in Penicillium chrysogenum and Penicillium oxalicum and using a transannular rearrangement to the desired triazaspirocycle 15. No abstract available
- |||||||||| Ampion (diketopiperazine) / Ampio
Journal: Isocoumarindole A, a Chlorinated Isocoumarin and Indole Alkaloid Hybrid Metabolite from an Endolichenic Fungus Aspergillus sp. (Pubmed Central) - Aug 1, 2019
The structure of isocoumarindole A (1) was featured by an unprecedented skeleton containing chlorinated isocoumarin and indole diketopiperazine alkaloid moieties linked by a carbon-carbon bond, which was determined by a combination of spectroscopic analyses, Marfey's method, and calculations of NMR chemical shifts, ECD spectra, and optical rotation values. Isocoumarindole A showed significant cytotoxicity and mild antifungal activities.
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Journal: Pyrroloindoline cyclization in tryptophan-containing cyclodipeptides mediated by an unprecedented indole C3 methyltransferase from Streptomyces sp. HPH0547. (Pubmed Central) - Jul 31, 2019
Diverse bioactive alkaloids with a tryptophan 2,5-diketopiperazine (DKP) core and an annulated structure forming a methylated pyrroloindoline-DKP assembly have been isolated from various microbial sources...Structural elucidation of the products revealed that this enzyme catalyzed unique pyrroloindoline cyclization in tryptophan-containing cyclodipeptides. This is the first C3 methyltransferase reported to catalyze pyrroloindoline cyclization in cyclic dipeptides, which provides a feasible and simple method to access diverse alkaloids.
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Journal: Secondary metabolites of Streptomyces sp. A1693 (Pubmed Central) - Jul 21, 2019
...The compounds comprised 5 butenolides，2 diketopiperazines，and 3 antimycin antibiotics...Among them，1 was defined as a new compound. All the compounds didn't show the cytotoxic activity against A549 cell line (IC₅₀>50 mg·L⁻¹).
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Journal: Uniaxial Alignment of a Monolayer of Flat-on Free-Base Porphyrins on an Exfoliable Insulating Substrate. (Pubmed Central) - Jul 12, 2019
The outcome of this work is represented by a unique crystal of mixed 2,5-diketepiperazine and fumaric acid in 1:1 ratio. We demonstrate that the (110) surface of this crystal fulfills the aforementioned requirements and, thanks to its peculiar sub-nanometric corrugations, allows to grow uniaxially aligned monolayers of flat-on porphyrin molecules assembled through van der Waals interactions.
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Journal: Monitoring the stabilities of a mixture of peptides by mass-spectrometry-based techniques. (Pubmed Central) - Jul 11, 2019
This demonstrates that the side-chain of the first amino acid has a significant influence on the stability of the Xaa-Pro sequence. From these data, we demonstrate the ability to simultaneously measure the dissociation kinetics and relative transition state thermochemistries for a mixture of peptides, which vary only in the identity of the N-terminal amino acid.
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Journal: Synthetic studies towards the penicisulfuranols: Synthesis of an advanced spirocyclic diketopiperazine intermediate. (Pubmed Central) - Jul 3, 2019
The 2,5-diketopiperazine (DKP) moiety is a core feature of many natural products and medicinally relevant scaffolds. As part of our efforts directed towards a total synthesis of penicisulfuranol B, we have developed and report herein: (1) the preparation of an N-hydroxy diketopiperazine intermediate accessible via a molybdenum-mediated oxidation of a parent diketopiperazine, and (2) further synthetic studies leading to a novel spirocyclic dihydrobenzofuran-containing diketopiperazine.
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Journal: De novo Biosynthesis of 'Non-Natural' Thaxtomin Phytotoxins. (Pubmed Central) - Jun 15, 2019
Thaxtomins are diketopiperazine phytotoxins produced by Streptomyces scabies and other actinobacterial plant pathogens that inhibit cellulose biosynthesis in plants...Upon feeding indole derivatives to the engineered S. albus strain, tryptophan intermediates with alternative substituents are biosynthesized and incorporated by the NRPS to deliver a series of thaxtomins with different functionalities in place of the nitro group. The approach described herein, demonstrates how genes from different pathways and different bacterial origins can be combined in a heterologous host to create a de novo biosynthetic pathway to 'non-natural' product target compounds.
- |||||||||| Ampion (diketopiperazine) / Ampio
Journal: Spectroscopic Evidence for Lactam Formation in Terminal Ornithine b and b Fragment Ions. (Pubmed Central) - Jun 12, 2019
Similarly, a comparison of the experimental IRMPD spectrum with calculated spectra shows that AAO b-ions also adopt a lactam structure, again with multiple different protonation sites, during fragmentation. This study provides spectroscopic confirmation for the lactam cyclization proposed for the "ornithine effect" and represents an alternative b structure to the oxazolone and diketopiperazine/macrocycle structures most often formed.
- |||||||||| Ampion (diketopiperazine) / Ampio
Journal: Cell-Penetrating Dynamic-Covalent Benzopolysulfane Networks. (Pubmed Central) - Jun 7, 2019
...Clearly better than and different to the reported diselenolanes and epidithiodiketopiperazines, we introduce the benzopolysulfanes (BPS), which show efficient delivery, insensitivity to inhibitors of endocytosis, and compatibility with substrates as large as proteins...Contrary to other COCs, BPS show high retention on thiol affinity columns. The identification of new modes of cell penetration is important because they promise new solutions to challenges in delivery and beyond.
- |||||||||| Ampion (diketopiperazine) / Ampio, diazepinomicin (AMO-01) / AMO Pharma
Journal: Whole Genome Sequencing and Metabolomic Study of Cave Streptomyces Isolates ICC1 and ICC4. (Pubmed Central) - May 28, 2019
One of the terpenes gene clusters predicted by antiSMASH possesses a seven-gene pathway consistent with diazepinomicin biosynthesis...The predicted similarities in molecule production and genome shared by these two strains could be an indicative of a cooperative mode of living in extreme habitats instead of a competitive one. This secondary metabolite potential may contribute to the fitness of ICC1 and ICC4 in the Iron Curtain Cave.
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Journal: Asenjonamides A-C, antibacterial metabolites isolated from Streptomyces asenjonii strain KNN 42.f from an extreme-hyper arid Atacama Desert soil. (Pubmed Central) - May 7, 2019
Bio-guided fractionation of the culture broth extract of Streptomyces asenjonii strain KNN 42.f recovered from an extreme hyper-arid Atacama Desert soil in northern Chile led to the isolation of three new bioactive β-diketones; asenjonamides A-C (1-3) in addition to the known N-(2-(1H-indol-3-yl)-2-oxoethyl)acetamide (4), a series of bioactive acylated 4-aminoheptosyl-β-N-glycosides; spicamycins A-E (5-9), and seven known diketopiperazines (10-16). All isolated compounds were characterized by HRESIMS and NMR analyses and tested for their antibacterial effect against a panel of bacteria.
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