Solid-phase synthesis of fullerene-peptides.
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.
Pantarotto
Davide
D
Department of Pharmaceutical Sciences, University of Trieste, Piazzale Europa 1, 34127 Trieste, Italy.
Bianco
Alberto
A
Pellarini
Federica
F
Tossi
Alessandro
A
Giangaspero
Anna
A
Zelezetsky
Igor
I
Briand
Jean-Paul
JP
Prato
Maurizio
M
D000596:Amino Acids / Q000737:chemistry; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000138:chemical synthesis; D004926:Escherichia coli / Q000187:drug effects; D005449:Fluorenes / Q000737:chemistry; D037741:Fullerenes / Q000737:chemistry* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D013211:Staphylococcus aureus / Q000187:drug effects
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D005449:Fluorenes; D037741:Fullerenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D009842:Oligopeptides; D004743:Enkephalin, Leucine