Therefore, these Foretinib purchase fullerene derivatives may also have potential as antibacterial agents. Figure 1 [Lys]-fullerene structure. Optimized structure of the [Lys]-fullerene. Methods Although C60 and C70 fullerenes are the most abundantly produced in carbon soot, higher fullerenes such as C76, C78, and C84 have also been isolated [24, 25] and are among the most abundant higher fullerenes [26]. We generate an initial C84 fullerene molecule using the fullerene library available in the Nanotube Modeler 1.7.3 software [27]. The C84 fullerene has six favorable isomers [28], and of these, the D2 and D2d have the lowest energy [29]. We choose the structure with D2d symmetry (structure number 23 in Nanotube Modeler) as this has also been reported

as the PF-6463922 most commonly observed in experiments [28]. The

C84 fullerene has an approximate diameter of 8 Å. Ideally, an ion channel blocker design would have flexible side chains which can bind to the channel and block the entrance this website to the pore. The D2d isomer of C84 has been shown to have the most localized π bonding of the fullerenes that have been isolated and has therefore been suggested as being the most reactive toward addition reactions [28]. Researchers [30–32] have also shown that it is possible to attach various chemical species to the outside of fullerene molecules. For example, phenylalanine and lysine amino acid derivatives have been attached to the C60 fullerene [30, 31]. Therefore, we Aprepitant import the C84 fullerene structure into ArgusLab 4.0.1 and attach six lysine derivatives to its outside surface [33]. A similar water-soluble amino-fullerene derivative with five cysteine moieties attached to the surface of C60 fullerene has previously been synthesized and characterized by Hu et al. [34]. They demonstrated the ability of this fullerene derivative to prevent oxidative-induced cell death without

evident toxicity [34]. We choose positively charged residues with the aim of mimicking the function of μ-conotoxin to NavAb. The distance between nitrogen atoms on opposing lysine chains is approximately 21 Å. The modified fullerene (C84(C4H8NH3 +)6 structure is optimized in ArgusLab [33] and is shown in Figure 1. The geometry optimizations were performed using default parameters, the Broyden-Fletcher-Goldfarb-Shanno algorithm and the universal force field. Restricted Hartree-Fock method was used, where the molecule is a closed shell system with all orbitals doubly occupied. All optimization processes are performed until the Hartree-Fock self-consistent field converged to 10−10 kcal/mol and the gradient converged to 10−1 kcal/mol/Å. Throughout this paper, this modified C84 fullerene is referred to as [Lys]-fullerene. The coordinates of NavAb are obtained from the protein database [PDB:3RVY] [35]. We obtain a homology model of Kv1.3 using the refined structure of the Kv1.2 channel (PDB:SLUT) as a template [36]. The generation of the homology model for Kv1.3 is described in detail in Chen et al.