Surface functionalization strategies for targeting nanoparticles (NP) to specific organs, cells, or organelles, is the foundation for new applications of nanomedicine to drug delivery and biomedical imaging. Interaction of NPs with biological media leads to the formation of a biomolecular layer at the surface of NPs so-called as "protein corona". This corona layer can shield active molecules at the surface of NPs and cause mistargeting or unintended scavenging by the liver, kidney, or spleen. To overcome this corona issue, we have designed biotin-cysteine conjugated silica NPs (biotin was employed as a targeting molecule and cysteine was used as a zwitterionic ligand) to inhibit corona-induced mistargeting and thus significantly enhance the active targeting capability of NPs in complex biological media. To probe the targeting yield of our engineered NPs, we employed both modified silicon wafer substrates with streptavidin (i.e., biotin receptor) to simulate a target and a cell-based model platform using tumor cell lines that overexpress biotin receptors. In both cases, after incubation with human plasma (thus forming a protein corona), cellular uptake/substrate attachment of the targeted NPs with zwitterionic coatings were significantly higher than the same NPs without zwitterionic coating. Our results demonstrated that NPs with a zwitterionic surface can considerably facilitate targeting yield of NPs and provide a promising new type of nanocarriers in biological applications.
So far, no detailed view has been expressed regarding the interactions between vancomycin and racemic compounds including mandelic acid. In the current study, a chiral stationary phase was prepared by using 3-aminopropyltriethoxysilane and succinic anhydride to graft carboxylated silica microspheres and subsequently by activating the carboxylic acid group for vancomycin immobilization. Characterization by elemental analysis, Fourier transform infrared spectroscopy, solid-state nuclear magnetic resonance, and thermogravimetric analysis demonstrated effective functionalization of the silica surface. R and S enantiomers of mandelic acid were separated by the synthetic vancomycin column. Finally, the interaction between vancomycin and R/S mandelic acid enantiomers was simulated by Auto-dock Vina. The binding energies of interactions between R and S enantiomers and vancomycin chiral stationary phase were different. In the most probable interaction, the difference in mandelic acid binding energy was approximately 0.2 kcal/mol. In addition, circular dichroism spectra of vancomycin interacting with R and S enantiomers showed different patterns. Therefore, R and S mandelic acid enantiomers may occupy various binding pockets and interact with different vancomycin functions. These observations emphasized the different retention of R and S mandelic acid enantiomers in vancomycin chiral column.
Five-component sequential Ugi/nucleophilic addition reaction of aromatic aldehydes, primary amines, propiolic acid, isocyanides, and hydrazides has been developed in order to access polyfunctional pseudopeptides. The reaction may proceed through formation of N-substituted 2-alkynamides as intermediates. This process is found to be mild and operationally simple with broad substrate scope.
In this study, we developed an efficient approach for the synthesis of 2-amino-1,3,4-oxadiazoles that are bioisosteres of the amide functional group. The synthesized oxadiazoles were conjugated to octa- and nonapeptides through the C- or N-terminus as precursors of leuprolide acetate. The synthesized compounds are peptidomimetics of leuprolide acetate.
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