Ala-Phe-OH

This paper focused on the mechanism of Ser-Ala-Gly-Pro-Ala-Phe (SAGPAF) treatment to improve gastric mucosal injury in mice. A gastric mucosa injury model induced by ethanol was established, and the superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, nitric oxide (NO) content and myeloperoxidase (MPO) level were determined. We performed macroscopic and histopathological evaluation of the gastric organs. Moreover, we analyzed the mechanism of SAGPAF treatment by western blotting. Compared with the model group, the SOD activity and NO content in the medium-dose and high-dose SAGPAF groups of treated with 10 kV cm-1 field intensity were significantly increased. The MDA content and MPO level were decreased significantly. They significantly reduced the gastric mucosal injury induced by ethanol (21.17 ± 3.51% and 13.99 ± 2.00%) and the histopathological scores (3.83 ± 0.40 and 4.33 ± 0.37) (P < 0.05). Western blotting analysis showed that SAGPAF after pulsed electric field (PEF) treatment improved gastric injury by reducing protein phosphorylation. These findings provided strong evidence that PEF-treated SAGPAF enhanced the gastric mucosal barrier function by inhibiting the activation of the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathways, reducing the ethanol-induced inflammatory response and oxidative stress.

The melanocortin receptors are involved in numerous physiological functions and are regulated by agonists derived from the proopiomelanocortin gene transcript and two endogenous antagonists, agouti and agouti-related protein (AGRP). The key binding and functional determinant of AGRP, an MC3R and MC4R antagonist, is an Arg-Phe-Phe tripeptide sequence located on an exposed hexapeptide (Arg-Phe-Phe-Asn-Ala-Phe) loop. It has previously been observed that cyclizing this sequence through a DPro-Pro motif (c[Pro1-Arg2-Phe3-Phe4-Asn5-Ala6-Phe7-DPro8]) resulted in a macrocyclic scaffold with MC4R antagonist activity, with increased MC4R potency when a diaminopropionic acid (Dap) residue is substituted at position 5. In this report, a series of 11 single-peptoid substitutions were performed in the AGRP-derived macrocycles. While most peptoid substitutions decreased MC4R antagonist potency, it was observed that NPhe4 (compounds 4 and 11) or NDab5 (diaminobutyric acid, compound 7) maintained MC4R antagonist potency. The NPhe4 substitutions also resulted in MC5R antagonist and inverse agonist activity equipotent to the parent scaffolds. These data may be used in the design of future MC4R and MC5R antagonist leads and probes that possess increased metabolic stability due to the presence of peptoid residues.

Burkholderia arboris, which belongs to the Burkholderia cepacia complex, has been shown to possess antifungal activity against several plant fungal pathogens; however, the antifungal compounds are yet to be identified. Here, we identified the antifungal compounds produced by B. arboris using genetic and metabolomic approaches. We generated a Tn5 transposon mutation library of 3,000 B. arboris mutants and isolated three mutants with reduced antifungal activity against the plant fungal pathogen Fusarium oxysporum. Among the mutants, the M464 mutant exhibited the weakest antifungal activity. In the M464 genome, the transposon was inserted into the cobA gene, encoding uroporphyrin-III methyltransferase. Deletion of the cobA gene also resulted in reduced antifungal activity, indicating that the cobA gene contributed to the antifungal activity of B. arboris. Furthermore, a comparison of the differential metabolites between wild type B. arboris and the ∆cobA mutant showed a significantly decreased level of tetrapeptide His-Ala-Phe-Lys (Hafk) in the ∆cobA mutant. Therefore, a Hafk peptide with D-amino acid residues was synthesized and its antifungal activity was evaluated. Notably, the Hafk peptide displayed significant antifungal activity against F. oxysporum and Botrytis cinerea, two plant pathogens that cause destructive fungal diseases. Overall, a novel antifungal compound (Hafk) that can be used for the biocontrol of fungal diseases in plants was identified in B. arboris.