Dual Functional Microcapsule based on Monodisperse Short PEG Amphiphile for Drug Encapsulation and Protein Affinity Controlled Release

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A short monodisperse poly(ethylene glycol) (PEG) and a neutral organic rotamer conjugate TEG-BTA-2 amphiphile was designed for the construction of a stimuli-responsive switchable self-assembled structure for drug encapsulation by noncovalent interaction and targeted controlled delivery. A short PEG, tetraethylene glycol (TEG) was covalently attached with a neutral organic rotamer benzothiazole dye (BTA-2) affording the neutral TEG-BTA-2 (<500 D). The TEG-BTA-2 is self-assembled into a microsphere in an aqueous medium, but remarkably undergoes morphology change switching to a rice-like microcapsule for curcumin encapsulation. Curcumin-loaded microcapsules were stable in an aqueous solution, however, were noticed disintegrating upon the addition of BSA protein. This is possibly due to an interaction with BSA protein leading to a protein affinity-controlled curcumin release in a neutral PBS buffer. Moreover, cell internalization of the neutral amphiphile TEG-BTA-2 into A549 cells was observed by fluorescence microscopy, providing an opportunity for application as a molecular vehicle for targeted drug delivery and monitoring.

Natural Products That Contain Higher Homologated Amino Acids

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This review focuses on discussing natural products (NPs) that contain higher homologs of amino acids (homoAAs) in the structure as well as the proposed and characterized biosynthesis of these non-proteinogenic amino acids. Homologation of amino acids includes the insertion of a methylene group into its side chain. It is not a very common modification found in NP biosynthesis as approximately 450 homoAA-containing NPs have been isolated from four bacterial phyla (Cyanobacteria, Actinomycetota, Myxococcota, and Pseudomonadota), two fungal phyla (Ascomycota and Basidiomycota), and one animal phylum (Porifera), except for a few examples. Amino acids that are found to be homologated and incorporated in the NP structures include the following ten amino acids: alanine, arginine, cysteine, isoleucine, glutamic acid, leucine, phenylalanine, proline, serine, and tyrosine, where isoleucine, leucine, phenylalanine, and tyrosine share the comparable enzymatic pathway. Other amino acids have their individual homologation pathway (arginine, proline, and glutamic acid for bacteria), likely utilize the primary metabolic pathway (alanine and glutamic acid for fungi), or have not been reported (cysteine and serine). Despite its possible high potential in the drug discovery field, the biosynthesis of homologated amino acids has a large room to explore for future combinatorial biosynthesis and metabolic engineering purpose.

Covalent and Visible‐Light Photoswitchable Derivatives of the Potent Synthetic Opioid Isotonitazene and Other Nitazenes

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Isotonitazene belongs to a potent class of m-opioid receptor (µOR) ligands, known as nitazenes. The lack of knowledge surrounding this agonist and others in its class has sparked thorough re-investigations. To aid in these investigations, the purportedly covalent yet underexplored nitazene BIT was biochemically re-evaluated in this work, along with a newly synthesized analogue, Iso-BIT. Moreover, in the pursuit of understanding the mechanism, function, and interactions of µOR, this study involved developing photoswitchable derivatives of nitazene as potential probe molecules. Converting known ligands into azo-containing photoswitchable derivatives offers the opportunity to modulate ligand structure with light, allowing for photocontrol of compound activity. While photocontrol of µOR activity could not be entirely achieved, photophysical evaluation of these arylazobenzimidazole derivatives revealed a novel photoswitch scaffold that responds to visible light. Furthermore, azo-containing 2e and 3e emerged as promising nitazene derivatives that were able to form an exceptionally high fraction of covalent-ligand receptor complexes with wild-type µOR at physiological pH.