Current studies on materials that exhibit metamaterial properties are mainly focused on lithography-generated 2D substrates. Here we report the successful fabrication of 22 nm gold nanoparticle rings with and without a central nanoparticle assembled on Tobacco Mosaic Virus coat protein disks. These structures are one of the first examples of nanorings produced independently of a substrate and represent the first steps toward the realization of a solution-phase or coatings-based metamaterial.

A common challenge in nanotechnology is the fabrication of materials with well-defined nanoscale structure and properties. Here we report that a genetically engineered tobacco mosaic virus (TMV) coat protein (CP), to which a hexahistidine (His) tag was incorporated, can self-assemble into disks, hexagonally packed arrays of disks, stacked disks, helical rods, fibers, and elongated rafts. The insertion of a His tag to the C-terminus of TMV-CP was shown to significantly affect the self-assembly in comparison to the wild type, WT-TMV-CP. Furthermore, the His tag interactions attributed to the alternative self-assembly of His-TMV-CP can be controlled through ethanol and nickel-nitrilotriacetic acid (Ni-NTA) additions as monitored with atomic force microscopy.

Paromomycin analogue activity: Novel amphiphilic aminoglycosides are shown to inhibit clinically relevant deactivating enzymes, without undergoing significant deactivation themselves.

Aminoglycoside-coenzyme A conjugates are challenging synthetic targets because of the wealth of functional groups and high polarity of the starting materials. We previously reported a one-pot synthesis of amide-linked aminoglycoside-CoA bisubstrates. These molecules are nanomolar inhibitors of aminoglycoside N-6′-acetyltransferase Ii (AAC(6′)-Ii), an important enzyme involved in bacterial resistance to aminoglycoside antibiotics. We report here the synthesis and biological activity of five new aminoglycoside-CoA bisubstrates containing sulfonamide, sulfoxide, or sulfone groups. Interestingly, the sulfonamide-linked bisubstrate, which was expected to best mimic the tetrahedral intermediate, does not show improved inhibition when compared with amide-linked bisubstrates. On the other hand, most of the sulfone-and sulfoxide-containing bisubstrates prepared are nanomolar inhibitors of AAC(6′)-Ii. Keywordsantibiotic; inhibition; neamine; resistance Aminoglycosides are broad spectrum antimicrobials. Unfortunately, widespread resistance to aminoglycosides threatens the use of this important class of antibiotics, alone or in synergistic combination with β-lactams. Resistance to aminoglycosides occurs mostly via drug modifications by enzymes such as aminoglycoside N-6′-acetyltransferases (AAC(6′)s).-Wright and coworkers have shown that catalysis by AAC(6′)-Ii proceeds via an ordered bi-bi mechanism in which acetyl coenzyme A (AcCoA) binds before the aminoglycoside. Attack of the aminoglycoside 6′-NH 2 at the thioester of AcCoA is believed to generate a tetrahedral intermediate, which subsequently collapses to yield a 6′-Nacetylaminoglycoside and CoA (Fig. 1) CIHR Author Manuscript CIHR Author Manuscript CIHR Author ManuscriptWe recently reported the use of amide-linked aminoglycoside-CoA bisubstrate inhibitors as mechanistic and structural probes of (AAC(6′)s. An effective regio-and chemo-selective protocol for the direct N-6′-derivatization of unprotected aminoglycosides was used to synthesize these inhibitors in one-pot (Fig. 1, 1a-b)., These molecules exhibited nanomolar inhibition towards AAC(6′)-Ii and allowed crystallization of AAC(6′)-Ii in complex with an aminoglycoside derivative for the first time.To improve inhibition and to investigate whether AAC(6′)-Ii stabilizes the tetrahedral intermediate, we envisaged to prepare a second generation of bisubstrates containing either a sulfonamide, sulfoxide or sulfone, expected to better mimic the tetrahedral intermediate ( Fig. 1, 2a-b, 3a-b and 4a-b). We hypothesized that if stabilization of this intermediate is important, a better mimetic would lead to increased affinity for the enzyme. Oxidized sulfides were selected for their ease of preparation, the higher polarizability of the S=O bond compared to a carbonyl, and the tetrahedral geometry at the sulfur atom. Sulfonamides have previously been used to mimic the tetrahedral intermediates involved in enzymatic catalysis by proteases arginase, dihydroorotase, and isoleucyl tRNA synthetase (K i = 0.04 nM).The cry...

Four short ligands; cysteine, cysteamine, dithiothrietol and glycine are examined and compared in their ability to stabilize and assemble silver nanoparticles (AgNPs).