Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable ...in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. Peptide "drugs" initially played only the role of hormone analogs to balance disorders. Nowadays, they achieve numerous biomedical tasks, can cross membranes, or reach intracellular targets. The role of peptides in bio-processes can hardly be mimicked by other chemical substances. The article is divided into independent sections, which are related to either the progress in short peptide-based theranostics or the problems posing challenge to bio-medicine. In particular, the SWOT analysis of short peptides, their relevance in therapies of diverse diseases, improvements in (bio)synthesis platforms, advanced nano-supramolecular technologies, aptamers, altered peptide ligands and in silico methodologies to overcome peptide limitations, modern smart bio-functional materials, vaccines, and drug/gene-targeted delivery systems are discussed.
Reservoir flood control scheduling is a challenging optimization task, particularly due to the complexity of various constraints. This paper proposes an innovative algorithm design approach to ...address this challenge. Combining the basic walrus optimization algorithm with the adaptive ε-constraint method and introducing the SPM chaotic mapping for population initialization, spiral search strategy, and local enhancement search strategy based on Cauchy mutation and reverse learning significantly enhances the algorithm's optimization performance. On this basis, innovate an adaptive approach ε A New Algorithm for Constraints and Multi Strategy Optimization Improvement (ε-IWOA). To validate the performance of the ε-IWOA algorithm, 24 constrained optimization test functions are used to test its optimization capabilities and effectiveness in solving constrained optimization problems. Experimental results demonstrate that the ε-IWOA algorithm exhibits excellent optimization ability and stable performance. Taking the Taolinkou Reservoir, Daheiting Reservoir, and Panjiakou Reservoir in the middle and lower reaches of the Luanhe River Basin as a case study, this paper applies the ε-IWOA algorithm to practical reservoir scheduling problems by constructing a three-reservoir flood control scheduling system with Luanxian as the control point. A comparative analysis is conducted with the ε-WOA, ε-DE and ε-PSO (particle swarm optimization) algorithms.The experimental results indicate that ε-IWOA algorithm performs the best in optimization, with the occupied flood control capacity of the three reservoirs reaching 89.32%, 90.02%, and 80.95%, respectively. The control points in Luan County can reduce the peak by 49%.This provides a practical and effective solution method for reservoir optimization scheduling models. This study offers new ideas and solutions for flood control optimization scheduling of reservoir groups, contributing to the optimization and development of reservoir scheduling work.
“Diazo” not needed: The title reaction results in the rearrangement of oxonium ylides, which were prepared from readily available homopropargylic allylic ethers instead of diazo compounds, through ...two different mechanisms: a concerted 2,3‐sigmatropic rearrangement, or a stepwise 1,4‐allyl migration followed by a Claisen rearrangement (see scheme).
The first total syntheses of rubialatins A and B, two newly discovered naphthohydroquinone dimers, were achieved with high efficiency and elegancy through rationally designed biomimetic approaches. ...The tandem ring contraction/Michael addition/aldol reaction followed by oxidation enabled the rapid access of prerubialatin from readily available precursors, which then diverted into rubialatins A and B via epoxidation and photoinduced skeletal rearrangement, respectively. Moreover, several new rubialatin congeners were also obtained along the synthetic tour, some of which were proved to be authentic natural products.
Conventional methods utilizing
protein activity assay or
parasite survival to screen for malaria inhibitors suffer from high experimental background and/or inconvenience. Here, we introduce a ...yeast-based system to facilitate chemical screening for specific protein or pathway inhibitors. The platform comprises several isogeneic
strains that differ only in the target of interest, so that a compound which inhibits one strain but not the other is implicated in working specifically against the target. We used
NDH2 (PfNDH2), a type II NADH dehydrogenase, as a proof of principle to show how well this works. Three isogenic
strains harboring, respectively, exogeneously introduced PfNDH2, its own complex I (a type I NADH dehydrogenase), and PfNDH2 with its own complex I, were constructed. In a pilot screen of more than 2,000 compounds, we identified a highly specific inhibitor that acts on PfNDH2. This compound poorly inhibits the parasites at the asexual blood stage; however, is highly effective in repressing oocyst maturation in the mosquito stage. Our results demonstrate that the yeast cell-based screen platform is feasible, efficient, economical, and has very low background noise. Similar strategies could be extended to the functional screen for interacting molecules of other targets.
Herein, we report the enantioselective total synthesis of dysiherbols A, C, and D, a unique group of 6/6/5/6/6 pentacyclic quinone/hydroquinone sesquiterpenes, featuring a photo-induced ...quinone–alkene 2 + 2 cycloaddition and a tandem 1,2-anionic rearrangement/cyclopropane fragmentation as key elements. Based on our total synthesis, the originally proposed structures of dysiherbols C and D have been revised. Detailed computational studies were carried out to gain deep insight into the unprecedented 1,2-anionic rearrangement, which revealed that the transformation, albeit a symmetry-forbidden process, proceeded through a concerted manner owing to the release of high ring-strain energy and the evolution of local aromaticity in the transition state. Taking all, the present work offers a mechanistically interesting and synthetically useful approach to accessing dysiherbols and related congeners.
RO8191 represents a newly identified small-molecule IFN-α-substitute, which displays potent anti-HCV activity. In this communication, we reported the design and synthesis of two series of ...imidazo1,2-α1,8naphthyridine derivatives, as RO8191 analogues, via a direct C-H arylation approach. Notably, by adjusting the reaction conditions, we could achieve the two series of analogues via regioselective single- and double-arylations, respectively. The anti-HCV activities of the synthesized compounds were evaluated within the HCV cell culture system, and the preliminary results showed that some of them displayed promising anti-HCV activities.
Cytochalasans are an important class of fungal metabolites displaying remarkable structural diversity and significant biological activity. Historically, considerable effort has been devoted toward ...the synthesis of cytochalasans. Comparably, merocytochalasans, an array of more complicated molecules biosynthetically derived from cytochalasans and epicoccine through hetero-dimerization, -trimerization or -tetramerization, have been less explored. In recent years, our group has shown keen interest on cytochalasans and merocytochalasans, which has culminated in the collective syntheses of a variety of representative molecules of this family. To this end, we first developed a highly concise, efficient and modular approach to access 11/6/5 tricyclic cytochalasans, featuring an intermolecular Diels-Alder reaction and a ring-closing metathesis reaction as key steps. Based on this synthetic route, several cytochalasan monomers, including aspochalasin B, aspochalasin P, aspochalasin D and aspergillin PZ, have been synthesized within 11–14 longest linear steps. Subsequently, a couple of hetero-dimeric and -trimeric merocytochalasans, including asperchalasines A-E and asperflavipine B, have been accessed from aspochalasin B and the suitable epicoccine precursors through a series of intriguing bio-inspired transformations such as Diels-Alder reaction and formal 5 + 2 cycloaddition. Moreover, the full profile of the regio- and endo/exo selectivity of the Diels-Alder heterodimerization has been explored through computational study. The present study not only notably enriches the synthetic chemistry of cytochalasans and merocytochalasans, but also affords venerable clue to decipher the biosynthetic origins of the newly identified merocytochalasans.
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The total synthesis of the structurally unique secondary metabolite sporolide B (1b) is described. The total synthesis of 1b was developed on the basis of preliminary studies that revealed the ...reactivity of an appropriate o-quinone as a diene system toward a number of indene derivatives as dienophiles, first in intermolecular and thence intramolecular settings. Thus, substrates were devised (37 and 75) that underwent exquisite intramolecular 4+2 cycloaddition reactions under thermal conditions to provide primitive sporolide-type structures that were subsequently elaborated to a sporolide model system, 9-epi-sporolide B, and 1b. The requisite indene o-quinone precursor 75 was synthesized through a ruthenium-catalyzed 2+2+2 cycloaddition reaction between a propargylic alcohol and a chloroacetylenic cyclopentenyne, followed by elaboration and silver-promoted oxidation of the resulting chloroindene derivative. In addition to the total synthesis of 1b, this work demonstrated, for the first time, the power of the intramolecular hetero 4+2 cycloaddition reaction in the total synthesis of complex molecules and the application of the ruthenium-catalyzed 2+2+2 cycloaddition reaction to highly substituted indene systems possessing a chlorine residue on the aromatic nucleus.
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