Platinum-binding peptides: understanding of selective binding and multifunctionality

Platinum-binding peptides have been used for fabrication of complex platinum nanomaterials such as catalysts, metallopharmaceuticals, and electrodes. In this review, we present understanding of the mechanisms behind platinum-binding (Pt-binding) peptides and the applications of the peptides as multifunctional biomaterials. We discuss how the surface recognition, the roles of individual amino acids, and arrangement of amino acid sequences interplay. Our summary on the current state of understanding of Pt-binding peptides highlights opportunities for interdisciplinary research which will expand the applicability of these multifunctional Pt-binding peptides.

Synthesis of a Large-Cavity Carbazole Macrocycle for Size-Dependent Recognition

A large-cavity carbazole macrocycle (1) is reported through condensation of a long and rigid monomer and paraformaldehyde. 1 exhibits highly selective binding of large-sized tetra(n-propyl) ammonium cation 3+. The complexation...

In Vivo Imaging With Two-Photon Microscope For Assessing Tumor Selective Binding Of Anti-CD137 Switch Antibody

STA551, a novel anti-CD137 switch antibody, binds to CD137 in an extracellular ATP (exATP) concentration dependent manner. Although STA551 was assumed to show higher target binding in tumor than normal tissues, quantitative detection of the target binding of switch antibody in vivo is technically challenging. In this study, we investigated the target binding of STA551 in vivo using intravital imaging with two-photon microscopy. Tumor-bearing human CD137 knock-in mice were intravenously administered 1 mg/kg of fluorescent-labeled antibodies at day 0 and 3. Flow cytometry analysis of antibody-binding cells and intravital imaging using two-photon microscopy was conducted at day4. Higher CD137 expression in tumor than spleen was detected by flow cytometry analysis, and T cells and NK cells were major CD137 expressing cells. In the intravital imaging experiment, conventional and switch anti-CD137 antibody showed binding in tumor. However, in spleen, the fluorescence of switch antibody was much weaker than conventional anti-CD137 antibody and comparable with isotype control. In conclusion, we could assess switch antibody biodistribution in vivo through intravital imaging with two-photon microscopy. These results suggested that the tumor selective binding of STA551 leads to a wide therapeutic window and potent antitumor efficacy without systemic immune activation.

Mechanism of actin-dependent activation of nucleotidyl cyclase toxins from bacterial human pathogens

Bacterial human pathogens secrete initially inactive nucleotidyl cyclases that become potent enzymes by binding to actin inside eukaryotic host cells. The underlying molecular mechanism of this activation is, however, unclear. Here, we report structures of ExoY from Pseudomonas aeruginosa and Vibrio vulnificus bound to their corresponding activators F-actin and profilin-G-actin. The structures reveal that in contrast to the apo-state, two flexible regions become ordered and interact strongly with actin. The specific stabilization of these regions results in an allosteric stabilization of the nucleotide binding pocket and thereby to an activation of the enzyme. Differences in the sequence and conformation of the actin-binding regions are responsible for the selective binding to either F- or G-actin. Other nucleotidyl cyclase toxins that bind to calmodulin rather than actin undergo a similar disordered-to-ordered transition during activation, suggesting that the allosteric activation-by-stabilization mechanism of ExoY is conserved in these enzymes, albeit the different activator.