Total synthesis in solution of alamethicin F50/5 by an easily tunable segment condensation approach

• Published in: Biopolymers Vol. 76; no. 6; pp. 485 - 493
• Main Authors: Peggion, Cristina, Coin, Irene, Toniolo, Claudio
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 2004
• Subjects: alamethicin; Alamethicin - chemical synthesis; Alamethicin - chemistry; Amino Acid Sequence; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Circular Dichroism; glutamine; Methods; Molecular Sequence Data; peptaibol; peptide synthesis in solution; segment condensation approach; Solutions; Spectroscopy, Fourier Transform Infrared
• ISSN: 0006-3525; 1097-0282
• DOI: 10.1002/bip.20161

A total synthesis in solution of the 19‐mer peptide component F50/5 of alamethicin, the most extensively investigated among the channel‐former peptaibol antibiotics, is reported. Three peptide segments (A, B, C) were prepared and assembled, followed by incorporation of the acetylated N‐terminal amino acid. The synthetic modules B and C are characterized by three Glu(OMe) residues (at positions 7, 18, and 19) that, after completion of the synthesis, were reacted with ammonia to provide alamethicin F50/5. By use of this general strategy, we also prepared the [Gln7, Glu(OMe)18,19] alamethicin F50/5 analogue. The purity and conformation of the final products were assessed by chromatographic, spectrometric, and spectroscopic techniques. This tunable segment condensation approach will pave the way for an easy synthesis of alamethicin analogues bearing amino acid residues with desired side‐chain probes even at the N‐terminus and in internal positions of the sequence. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2004