The solid-phase synthesis of peptides (SPPS) containing [60]fullerene-functionalized amino acids is reported. A new amino acid, fulleropyrrolidino-glutamic acid (Fgu), is used for the SPPS of a series of analogues of different length based on the natural Leu(5)-Enkephalin and on cationic antimicrobial peptides. These fullero-peptides were prepared on different solid supports to analyze the influence of the resin on the synthesis. Optimized protocols for the coupling and deprotection procedures were determined allowing the synthesis of highly pure peptides in sufficient quantities for evaluation of biological activities. In particular, to avoid side reactions of the fullerene moiety with bases and nucleophiles, the removal of the protecting groups was performed under inert conditions (nitrogen or argon in the dark). We have encountered serious problems with the recovery of the crude compounds, especially when Fgu was inserted in the proximity of the resin core as fullero-peptides tend to remain embedded inside the resin. Eventually, all of the fullero-peptides were easily purified, and the cationic peptides were tested for their antimicrobial activities. They displayed a specific activity against the Gram-positive bacterium S. aureus and also lysed erythrocytes. The availability of a fullero-amino acid easily useable in the SPPS of fullero-peptides may thus open the way to the synthesis of new types of biologically active oligomers.

We report the synthesis of three novel, versatile fullerene intermediates whose main feature is the presence of an amino end group. Simple condensation reactions of these intermediates under standard conditions produce new derivatives that are useful for applications in materials science and medicinal chemistry.

Four ionic fullerene derivatives, which are relatively soluble in polar solvents, are shown to organize into morphologically different nanoscale structures. Spheres, nanorods, and nanotubules form in water depending on the side chain appendage of the fullerene spheroid. Images at different nanoscale structures were obtained via transmission electron microscopy. Also, computer simulations were used for investigating the relative spatial arrangements. The efficient method to fabricate almost perfect and uniformly shaped nanotubular crystals, which order spontaneously by self-assembly, opens the way to the possibility of exploiting the fullerene properties at the nanometer scale.T he ability to engineer distinct one-, two-, or threedimensional patterns at the supramolecular level by modifying specific chemical components is a crucial step toward nanometer-sized technology (1, 2). Preliminary and successful methodologies have yielded a large variety of noncovalently bonded structures in solutions and crystals. However, the possibility of regulating size and shape of nanostructures in relation to function remains a current challenge of exceptional interest (3-9). It is therefore expected that the rules of nanopatterning of organic molecules, either spontaneous or induced, once understood, can play a major role in future and emerging technologies.Fundamental requisites, accompanying the addition of welldesigned chemical functionalities to drive self-assembly processes to (pre)determined mesoscopic shapes of controlled sizes and outer-shell structures, are the conservation, and possibly even the enhancement, of the molecular level properties. To this end, fullerenes are ideal candidates, both because of their excellent electronic properties-most of their derivatives have so far shown to be outstanding electron acceptors (10-15)-and because their amphiphilic derivatives were recently found to self-assemble at the nanometer scale to furnish nanorod and vesicle patterns (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). Fullerenes, in fact, have a strong tendency to form clusters of different sizes, especially in polar solvents (27,28). Aggregation of C 60 units may cause a significant change in their photochemical and photophysical properties, as compared with isolated molecules in solution (12). Of course, this change can have a profound influence on fullerenebased optical and electronic materials (29,30). For instance, aggregation of fullerene spheroids was shown to play a crucial role in the preparation of photovoltaic cells (31).Also, biological tests of fullerenes, which are usually carried out in aqueous solutions, are heavily affected by aggregation (32). Basically, dissolution of unmodified C 60 or monofunctionalized organofullerenes is always accompanied by a high degree of clustering.Here, we show that the hydrophobic fullerene core, combined with hydrophilic ammonium groups and also with other selforganizing groups, assembles into three fundamentally different low-dimensional shapes and, in particular, it is demons...

[see structure]. A fullerene derivative containing a free amino group has been condensed with N-Fmoc-L-glutamic acid alpha-tert-butyl ester to give a C60-functionalized amino acid. The carboxylic end of this amino acid has been deprotected in acidic conditions, and the resulting acid has been used for solid-phase peptide synthesis. The final peptide, cleaved from the resin, was very soluble in water solutions and showed antimicrobial activity against two representative bacteria.