Assessment of the bioactive lipid profiles of oil extracted from Tunisian table olive cultivars (Barouni,Besbassi, and Marsaline cvs.)

Bioactive compounds are components extracted from biological matrices that may offer physiological health benefits and have nutritive value. The present study characterized bioactive lipid components such as fatty acids, phytosterols, policosanol, and triterpenes from table olives. The table olives were processed according to the green Spanish-style method. The obtained results indicate that phytosterol fraction constitutes the major portion of the total unsaponifiable matter. The analysis of phytosterols showed the presence of 11 compounds, β-sitosterol the predominant one. The policosanol composition indicated that hexacosanol, tetracosanol, octacosanol, and docosanol were the main compounds, accounting for over 85% of total policosanols. Pentacyclic triterpenes (cycloartenol and 24-methylene cycloartenol) were found at a higher level (over 85%) compared to tetracyclic triterpenes (β-amyrin, δ-amyrin). These findings reveal that processed table olives contain an interesting amount of various bioactive compounds compared to marine and other floral biological matrices. Thus, processed table olives represent an interesting natural functional food that presents high stability and bioavailability of their natural bioactive ingredients. Practical Applications: Nowadays, with health food gaining popularity among consumers, the demand for natural bioactive compounds and functional food is expanding considerably all over the world. This study focuses on analyzing bioactive lipid components from processed table olives. Fruits were processed according to the green Spanish-style method. The salt content of the brine was adjusted to the minimum sodium chloride value required by the Codex Alimentarius Comission, which is 5%, taking into consideration people suffering from hypertension. This concentration is considered the minimum amount of salt necessary to exhibit antibacterial activities. Considering the results obtained, processed table olives present one of the most valuable potential resources for bioactive lipid compounds and have a considerable ability to preserve the stability of their lipid components. Thus, the food industry in Mediterranean countries can promote processed table olives as conventional functional food with no need for any enrichment or fortification.     

A Degron Blocking Strategy Towards Improved CRL4CRBN Recruiting PROTAC Selectivity**

Small molecules inducing protein degradation are important pharmacological tools to interrogate complex biology and are rapidly translating into clinical agents. However, to fully realise the potential of these molecules, selectivity remains a limiting challenge. Herein, we addressed the issue of selectivity in the design of CRL4^CRBN recruiting PROteolysis TArgeting Chimeras (PROTACs). Thalidomide derivatives used to generate CRL4^CRBN recruiting PROTACs have well described intrinsic monovalent degradation profiles by inducing the recruitment of neo-substrates, such as GSPT1, Ikaros and Aiolos. We leveraged structural insights from known CRL4^CRBN neo-substrates to attenuate and indeed remove this monovalent degradation function in well-known CRL4^CRBN molecular glues degraders, namely CC-885 and Pomalidomide. We then applied these design principles on a previously published BRD9 PROTAC (dBRD9-A) and generated an analogue with improved selectivity profile. Finally, we implemented a computational modelling pipeline to show that our degron blocking design does not impact PROTAC-induced ternary complex formation. We believe that the tools and principles presented in this work will be valuable to support the development of targeted protein degradation.