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The deletion of the C-terminal arginine of the anaphylatoxin protein C5a reduces it receptor binding affinity. Understanding how C-terminal arginine affects the structure and bioactivity of C5a is important for the development of C5a C-terminal mimics as drug candidates. Herein, we report the total chemical synthesis of rat C5a and its d -enantiomer with its C-terminal arginine deleted, namely l -rC5a-desArg and d -rC5a-desArg. The structure of rC5a-desArg was then determined by racemic crystallography for the first time. The C-terminal residues of rC5a-Arg were found to expand from the fourth helix in a continuous helical conformation. This C-terminal conformation is significantly different from that of the previously reported full-length of C5a, indicating that the deletion of C-terminal arginine residue could result in the destruction of a positively charged surface formed by two adjacent Arg residues in C5a.

A novel donor-acceptor (D-A) type of two-photon (TP) fluorescent probe, i.e. Lyso-OSC, based on the lysosome-targeting morpholine group was developed. The polarity sensing coumarin group was functionalized as the acceptor and the 1-vinyl-4-methoxybenzene group was engineered as the donor. The fluorescence intensity and emission maximum wavelength of Lyso-OSC are highly sensitive to the polarity changes of solvent. The two-photon absorption cross-section and tissue penetration depth are up to 254 GM and 150 μm, respectively. The strong fluorescence, high sensitivity to polarity, low cytotoxicity, and accurate lysosome-targeting ability entail Lyso-OSC the excellent performance in detecting the polarity changes of cellular environment. To this end, a bright, real-time imaging autophagy of living cells has been achieved.

Solid-phase incorporation of diaminodiacids is one of the most effective approaches for synthesis of peptide disulfide bond mimics. One of a limitation of current diaminodiacid toolbox is that only four-atom linkage mimics are available that may not fully meet the activity optimization requirement. In this work, we developed a new diaminodiacid that contains a five-atom thioether (C–C–S–C–C) bridge for the first time. With this diaminodiacid in hand, we successfully obtained oxytocin containing new disulfide bond mimic by solid phase peptide synthesis.

The East African Rift System (EARS) is thought to be an intra-continental ridge that meets the Red Sea and the Gulf of Aden at the Ethiopian Afar as the failed arm of the Afar triple junction. The geodynamics of EARS is still unclear even though several models have been proposed. One model proposes that the EARS developed in a local tensile stress field derived from far-field loads because of the pushing of oceanic ridges. Alternatively, some scientists suggest that the formation of the EARS can be explained by upwelling mantle plumes beneath the lithospheric weak zone (e.g., the Pan-African suture zone). In our study, a shell model is established to consider the Earth’s spherical curvature, the lithospheric heterogeneity of the African continent, and the coupling between the mantle plumes and the mid-ocean ridge. The results are calculated via the finite element method using ANSYS software and fit the geological evidence well. To discuss the effects of the different rock mechanical parameters and the boundary conditions, four comparative models are established with different parameters or boundary conditions. Model I ignores the heterogeneity of the African continent, Model II ignores mid-ocean spreading, Model III ignores the upwelling mantle plumes, and Model IV ignores both the heterogeneity of the African continent and the upwelling mantle plumes. Compared to these models is the original model that shows the best-fit results; this model indicates that the coupling of the upwelling mantle plumes and the mid-ocean ridge spreading causes the initial lithospheric breakup in Afar and East Africa. The extension direction and the separation of the EARS around the Tanzanian craton are attributed to the heterogeneity of the East African basement.

Thioether-bonded bicyclic peptide can resist proteolytic degradation and become a promising scaffold for peptide-based inhibitor discovery. Chemical synthesis of thioether-bonded bicyclic peptide usually requires two orthogonal Cys protecting groups. Here, we report an efficient strategy for its preparation by using the commonly used Trt-protected and StBu-protected cysteines. Due to the thiol-disulfide exchange, S-StBu group is generally considered incompatible with sulfhydryl group under neutral conditions. We find that, in DIPEA-containing DMF solution, the peptide that contains both sulfhydryl and S-StBu groups can undergo selective thiol bisalkylation while maintaining the integrity of the S-StBu groups. In our strategy, the formation of two thioether bonds are both conducted in solution, and can be easily tracked by HPLC, which may be beneficial for the chemical synthesis of thioether-bonded bicyclic peptides.

Thioether-bonded cyclic peptide is widely present in current peptide-based drug discovery, and the diversification of its topological structure is conducive to the optimization of its biological activity. In this paper, we report a facile strategy for the synthesis of thioether-bonded head-to-tail cyclized peptides containing cross-linking arms of different length. The key of our strategy is the development of AMDMBT-based 2-chlorotrityl resins, which are prepared by the treatment of 2-chlorotrityl chloride resin with aminoethanethiol, dibromomethylbenzene and dithiol. The AMDMBT 2-chlorotrityl resin allows us to conveniently obtain peptides containing bromoacetyl group at the N-terminus and structurally diverfied sulfhydryl group at the C-terminus. The peptides can undergo head-to-tail cyclization in solution to form thioether-bonded head-to-tail cyclized peptides. The reported method will facilitate the in-depth optimization of the structure and activity of thioether-bonded head-to-tail cyclized peptides.

Pokkah boeng disease (PBD) is a foliar disease causing severe losses in sugarcane crop production. Research into resistance mechanisms against the causal agent, Fusarium verticillioides, is particularly important for farmers and researchers. This work based on the comprehensive analysis of metabolic, proteomic, and bioinformatics data on nitrogen (N) metabolism, which revealed that this biosynthetic reactions was closely related to resistance mechanisms in the sugarcane– F. verticillioides interaction. Our results suggested that pathogen infection reduced the suppression of nitrate reductase (NR) activity, reducing ammonium nitrogen (NH4+-N) and nitrate nitrogen (NO3−-N) assimilation, which reduces glutamine synthetase (GS), glutamate synthetase (GOGAT) activity and polynucleotide synthesis and promotes RNA degradation, resulting in a decrease in ribosome levels and protein synthesis. Cysteine was found to be associated with the symptoms of PBD, while alanine, lysine, proline, and glutamic acid were found to be involved in protective and regulatory mechanisms as well. Additionally, glutamate played an important role in sugarcane defense against pathogens through the biosynthesis of proline and polyamines. Cyanamide, glutamate, proline, tyrosine, and arachidonic acid metabolism actively participate in resistance and response to stress. C5XPZ6 and C5XCA6 were considered to be critical proteins and key effectors according to this study. In conclusion, we have identified potential proteins and pathways involved in sugarcane resistance to F. verticillioides, revealing new findings that may be useful in the design of future diagnostics or sugarcane protection strategies and providing new insights into the molecular mechanisms of sugarcane–pathogen interactions.

The Mesozoic African rift system is an important continental rift system related to the Central African Shear Zone. While several geological models have been discussed, the mechanism of the Mesozoic African rift system is still unclear. One model proposed that the mechanism of the Mesozoic African rift system was inherited from the Benue Trough, which is a failed arm of the Guinea triple junction. Other models suggested that the mechanism of the Mesozoic African rift system could be clarified by the spreading of the Atlantic and weak lithospheric zones, such as the Pan-African suture zone. In this research paper, we create a shell model that considers spherical curvature, the heterogeneous structure of the African basement framework, and a combination of the upwelling St. Helena plume and seafloor spreading. The calculation of the model is solved through the finite element software ANSYS, and the modeling results match the actual geological evidence. In this study, nine other models are created with altered rock parameters or boundary constraints and compared to the original model to examine the influence of these factors. Compared to the nine comparative models, the original model best reflects the calculated results, which indicates that the coupling of the St. Helena mantle plume and ocean-ridge spreading caused the initial lithospheric rifting at ∼130 Ma and that the heterogeneities within Africa did not affect the extension direction of the rift basin but did influence the location of the rift basin.