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Simple Summary: In this study, we applied translational informatics for intelligent medicine of acute myeloid leukemia, a type of cancer characterized by disease relapses even after seemingly successful treatments. Treatment failure is associated, at least in part, with the fact that targeting individual proteins often promotes rewiring of relevant networks and re-organization of interactions of, among others, non-targeted proteins to eventually evade single-target therapies. To develop efficient therapies, these dynamics should be taken into account and target whole network modules instead of singleton genes in order to prevent the establishment of compensating signaling circuits. Therefore, we integrated network-based methods, structural pharmacology, and molecular modeling to establish two complementary multitargeting strategies, one in the form of repurposable drug combinations and the other as a de novo synthesized triple-targeting agent. Of note, our study exploits, for the first time, a greedy algorithm to identify optimal combinations of drugs and therapeutic protein targets. Background/Objectives: Acute myeloid leukemia (AML) is characterized by therapeutic failure and long-term risk for disease relapses. As several therapeutic targets participate in networks, they can rewire to eventually evade single-target drugs. Hence, multi-targeting approaches are considered on the expectation that interference with many different components could synergistically hinder activation of alternative pathways and demolish the network one-off, leading to complete disease remission. Methods: Herein, we established a network-based, computer-aided approach for the rational design of drug combinations and de novo agents that interact with many AML network components simultaneously. Results: A reconstructed AML network guided the selection of suitable protein hubs and corresponding multi-targeting strategies. For proteins responsive to existing drugs, a greedy algorithm identified the minimum amount of compounds targeting the maximum number of hubs. We predicted permissible combinations of amiodarone, artenimol, fostamatinib, ponatinib, procaine, and vismodegib that interfere with 3–8 hubs, and we elucidated the pharmacological mode of action of procaine on DNMT3A. For proteins that do not respond to any approved drugs, namely cyclins A1, D2, and E1, we used structure-based de novo drug design to generate a novel triple-targeting compound of the chemical formula C15H15NO5, with favorable pharmacological and drug-like properties. Conclusions: Overall, by integrating network and structural pharmacology with molecular modeling, we determined two complementary strategies with the potential to annihilate the AML network, one in the form of repurposable drug combinations and the other as a de novo synthesized triple-targeting agent. These target–drug interactions could be prioritized for preclinical and clinical testing toward precision medicine for AML. [ABSTRACT FROM AUTHOR]

Primary and secondary amines selectively react with the lactone moiety of γ-valerolactone oxide (GVLO). Several primary amines afforded the resulting epoxyamides with an intact epoxy group. In some cases addition of two equivalents of amine resulted in additional epoxide opening to give α,γ-dihydroxy-β-amino-amides. The selective lactone-opening in GVLO was further corroborated by DFT-studies. [ABSTRACT FROM AUTHOR]

As the production volume of polymers increases, so does the amount of plastic waste. Plastic recycling is one of the concepts to address in this issue. Unfortunately, only a small fraction of plastic waste is recycled. Even with the development of polymers for closed loop recycling that can be in theory reprocessed infinitely the inherent dilemma is that because of collection, cleaning and separation processes the obtained materials simply are not cost competitive with virgin materials. Chemical upcycling, the conversion of polymers to higher valuable products, either polymeric or monomeric, could mitigate this issue. In the following article, we highlight recent examples in this young but fast-growing field. This article is part of the theme issue 'Bio-derived and bioinspired sustainable advanced materials for emerging technologies (part 2)'. [ABSTRACT FROM AUTHOR]

Industrially relevant intermediates such as malonic acid, malonates and 3-oxopropionates can be easily accessed by ozonolysis of α-angelica lactone, derived from the platform chemical levulinic acid. The roles of the solvent and of the quenching conditions are of key importance for the outcome of the reaction. [ABSTRACT FROM AUTHOR]

Novel polyester polyols were prepared in high yields from biobased 1,4‐pentanediol catalyzed by non‐toxic phosphoric acid without using a solvent. These oligomers are terminated with hydroxyl groups and have low residual acid content, making them suitable for use in adhesives by polyurethane formation. The thermal behavior of the polyols was studied by differential scanning calorimetry, and tensile testing was performed on the derived polyurethanes. The results were compared with those of polyurethanes obtained with fossil‐based 1,4‐butanediol polyester polyols. Surprisingly, it was found that a crystalline polyester was obtained when aliphatic long‐chain diacids (>C12) were used as the diacid building block. The low melting point of the C12 diacid‐based material allows the development of biobased shape‐memory polymers with very low switching temperatures (<0 °C), an effect that has not yet been reported for a material based on a simple binary polyester. This might find application as thermosensitive adhesives in the packaging of temperature‐sensitive goods such as pharmaceuticals. Furthermore, these results indicate that, although 1,4‐pentanediol cannot be regarded as a direct substitute for 1,4‐butanediol, its novel structure expands the toolbox of the adhesives, coatings, or sealants formulators. [ABSTRACT FROM AUTHOR]