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Marine cyclic peptides have become an important source for drug development. In this work, two novel cyclic peptide zygosporamide analogs with the isoindolinone fragment were prepared, which have broad-spectrum antitumor activity. We have tried to compare their bioactivities by changing the amino acid (R-3Leu and S-4Leu) configuration. Notably, compound 8, with R-3Leu and S-4Leu residues, showed better inhibiting ability than that of compound 9, which contains S-3Leu and R-4Leu residues. Furthermore, careful molecular docking indicated that compound 8 presented stronger binding with the EGFR protein of liver cancer cells, providing an explanation for the difference in bioactivity. This research has provided a useful guide for peptide-based drug-target design. [ABSTRACT FROM AUTHOR]

A facile methodology for the synthesis of bicyclopeptides containing isoindolone was developed by an intramolecularly photo-induced electron transfer cyclo-reaction (IPETC) with high yield and stereoselectivity. Nine bisulfide-bridged bisisodindolone–cyclopeptides were successfully prepared based on the construction of an intramolecular bis-(donor–acceptor) electron system using L -cystine as the linker. The stereostructures of the bicyclopeptides were determined by ECD and 13C-NMR spectra combined with quantum chemistry calculations. The research provided a possible solution for the preparation of multi-cyclopeptides with complex and rigid cyclic structures by introducing cysteine moieties into linear peptides. [ABSTRACT FROM AUTHOR]

Two novel isoindole-doped cyclopeptide analogs of phakellistatin 2 with γ-turns were prepared. The compound with all D -Pro residues showed better antitumor activity against HepG-2 cells than that containing all L -Pro moieties, indicating the importance of the handedness of the conformation. LDH release tests showed that the compounds killed the cancer cells through a membrane disruption mechanism. [ABSTRACT FROM AUTHOR]

Two novel chiral cyclic peptide analogues of galaxamide were synthesized by photoinduced single electron transfer cyclization. Their stereochemistry was studied by experimental and theoretical ECD simulations. The title compounds were found to be active against HepG-2 cell lines (IC50 = 19.52 for 1 and 26.34 μg mL−1 for 2). [ABSTRACT FROM AUTHOR]

Two novel Fenestin A analogs (1 and 2) containing a phthalimide moiety are prepared by photoinduced cyclization. Their absolute configurations were determined by experimental ECD with the aid of theoretical calculations. The resulting compounds are active in HeLa (IC50 = 28.2 μM for 1 and 36.5 μM for 2) and HepG-2 cell lines (IC50 = 33.5 μM for 1 and 40.3 μM for 2). [ABSTRACT FROM AUTHOR]

Cyclic peptides have become a powerful modality in drug development. Naturally isolated cyclic peptides such as phakellistatins have been found to have broad-spectrum bioactivity. In this paper, we have prepared an analog of phakellistatin 18, and tried to compare its bioactivity with that of our reported phakellistatin 2 analog. It was found that compound 1 derived from phakellistatin 18 showed inferior inhibiting ability compared to the phakellistatin 2 analog, similar to the phenomenon observed in the natural products (phakellistatin 2 presented stronger antitumor activity than that of phakellistatin18). We have performed molecular docking of the two analogs with the MDM2 protein using AutoDock Tools, which showed that the phakellistatin 2 analog presented stronger binding through a H-bond, providing an explanation for the bioactivity difference. [ABSTRACT FROM AUTHOR]

Electrochemical water splitting is considered a green and sustainable method of producing hydrogen energy. Herein, to pursue a highly efficient hydrogen evolution reaction, we fabricated high-performance electrocatalysts, by utilizing a bimetallic (Cu and Co) metal–organic framework to modify rGO through a one-step in situ approach. The synthesized CuCoOC@rGO presents a highly ordered structure with a defect-rich porous surface for the hydrogen evolution reaction (HER). Specifically, the appropriate adjustment of metal (Cu and Co), 1,3,5-benzenetricarboxylic acid (H3BTC), and rGO ratios leads to a well-defined morphology, which creates a defect-rich porous surface. Characterized by XRD, SEM, EDS, FT-IR spectroscopy, Raman spectroscopy, XPS, and BET, the morphology exposes more active sites, strong evidence for the promotion of electrocatalytic efficiency. Upon the analysis of the experimental data, the obtained CuCoOC@rGO catalyst exhibits excellent activity in alkaline media with a low overpotential of 120 mV at a current density of 10 mA cm−2, and a Tafel slope of 124 mV dec−1 for the hydrogen evolution reaction (HER). Guided by the structure–activity relationship, the superior HER activity of CuCoOC@rGO in alkaline electrolyte could originate from many sources, including: (1) as a self-supported substrate, CuCoOC@rGO not only leads to profitable electrical contact and mechanical stability but also firmly roots into the rGO without extra binders. (2) The highly ordered structure provides smooth ion and electron transport channels, which are conducive to electrolyte infiltration and gas release. (3) The abundance of defective pores on the surface of the nanoarrays, which offers more active sites for the catalytic process. This study provides new prospects for the rational design and fabrication of advanced hierarchical functional electrocatalysts for application in electrochemical energy devices. [ABSTRACT FROM AUTHOR]