Improving Soluble Phenolic Profile and Antioxidant Activity of Grape Pomace Seeds through Fungal Solid-State Fermentation.

Grape pomace seeds contain abundant phenolic compounds, which are also present in both soluble and insoluble forms, similar to many other plant matrices. To further increase the extractable soluble phenolics and their antioxidant activities, grape pomace seeds were fermented with different fungi. Results showed that solid-state fermentation (SSF) with Aspergillus niger, Monascus anka, and Eurotium cristatum at 28 °C and 65% humidity had a significantly positive impact on the release of soluble phenolics in grape pomace seeds. Specifically, SSF with M. anka increased the soluble phenolic contents by 6.42 times (calculated as total phenolic content) and 6.68 times (calculated as total flavonoid content), leading to an overall improvement of antioxidant activities, including DPPH (increased by 2.14 times) and ABTS (increased by 3.64 times) radical scavenging activity. Furthermore, substantial changes were observed in the composition and content of individual phenolic compounds in the soluble fraction, with significantly heightened levels of specific phenolics such as chlorogenic acid, syringic acid, ferulic acid, epicatechin gallate, and resveratrol. Notably, during M. anka SSF, positive correlations were identified between the soluble phenolic content and hydrolase activities. In particular, there is a strong positive correlation between glycosidase and soluble phenols (r = 0.900). The findings present an effective strategy for improving the soluble phenolic profiles and bioactivities of grape pomace seeds through fungal SSF, thereby facilitating the valorization of winemaking by-products.

Discovery and Optimization of WDR5 Inhibitors via Cascade Deoxyribonucleic Acid-Encoded Library Selection Approach.

The DNA-encoded library (DEL) is a powerful hit generation tool for chemical biology and drug discovery; however, the optimization of DEL hits remained a daunting challenge for the medicinal chemistry community. In this study, hit compounds targeting the WIN binding domain of WDR5 were discovered by the initial three-cycle linear DEL selection, and their potency was further enhanced by a cascade DEL selection from the focused DEL designed based on the original first run DEL hits. As expected, these new compounds from the second run of focused DEL were more potent WDR5 inhibitors in the protein binding assay confirmed by the off-DNA synthesis. Interestingly, selected inhibitors exhibited good antiproliferative activity in two human acute leukemia cell lines. Taken together, this new cascade DEL selection strategy may have tremendous potential for finding high-affinity leads against WDR5 and provide opportunities to explore and optimize inhibitors for other targets.