Peggion Cristina, Coin Irene, Toniolo Claudio
Department of Chemistry, University of Padova, 35131 Padova, Italy.
Biopolymers. 2004;76(6):485-93. 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.
报道了在溶液中对19聚体肽组分阿拉米辛F50/5进行全合成，阿拉米辛是通道形成肽抗生素中研究最为广泛的一种。制备并组装了三个肽段（A、B、C），随后引入了乙酰化的N端氨基酸。合成模块B和C的特征在于三个Glu(OMe)残基（位于第7、18和19位），在合成完成后，它们与氨反应生成阿拉米辛F50/5。通过使用这种通用策略，我们还制备了[Gln7, Glu(OMe)18,19]阿拉米辛F50/5类似物。通过色谱、光谱和波谱技术对最终产物的纯度和构象进行了评估。这种可调节的片段缩合方法将为轻松合成在序列的N端以及内部位置带有具有所需侧链探针的氨基酸残基的阿拉米辛类似物铺平道路。
