GRAMICIDIN-S ANALOGS WITH A D-ALA, GLY, OR L-ALA RESIDUE IN PLACE OF THE D-PHE RESIDUE - MOLECULAR-CONFORMATIONS AND INTERACTIONS WITH PHOSPHOLIPID MEMBRANE
GRAMICIDIN-S ANALOGS WITH A D-ALA, GLY, OR L-ALA RESIDUE IN PLACE OF THE D-PHE RESIDUE - MOLECULAR-CONFORMATIONS AND INTERACTIONS WITH PHOSPHOLIPID MEMBRANE
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DOI：
10.1002/bip.360251207
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发表时间：
1986-12-01
期刊：
影响因子：
2.9
通讯作者：
NAGAI, U
中科院分区：
文献类型：
--
作者：
HIGASHIJIMA, T;MIYAZAWA, T;NAGAI, U
短杆菌肽 S (GS) [环状-(Val1,1''-Orn2,2''-Leu3,3''-D-Phe4,4''-Pro5,5'')2 和 GS 类似物.sbd.即 [D-Ala4,4'']-GS、[Gly-4,4'']-GS 和 分析了[L-Ala4,4'']-GS.sbd。 [D-Ala4,4'']-GS的分子构象与GS相似，D-Ala-Pro肽键为反式。 [Gly4,4'']-GS的分子构象取决于二甲亚砜-d6/三氟乙醇(DMSO-d6/TFE)和DMSO-d6/H2O的溶剂组成以及溶质浓度。在DMSO-d6溶液中，[Gly4,4'']-GS在较低浓度下形成单体的GS型构象。在较高浓度下，GS 型构象异构体转化为另一种形成分子聚集体的构象异构体。 DMSO-d6 中的 [Gly4,4'']-GS 和 [L-Ala4,4'']-GS 以及 TFE 溶液中的 [L-Ala4,4'']-GS 均发现 X-Pro 肽键的顺式形式。 DMSO-d6 溶液中[L-Ala4,4'']-GS 的α-质子化学位移的大温度依赖性表明共聚体平衡随温度变化。 [L-Ala4,4'']-GS 中不形成 GS 型构象。两种活性肽类似物 [D-Ala4,4'']-GS 和 [Gly4,4'']-GS 与磷脂膜相互作用，形成 GS 型构象。相比之下，无活性类似物 [L-Ala4,4'']-GS 不与磷脂膜相互作用。发现 GS 类似物的活性与与磷脂膜结合后 GS 型构象的形成相关。
The proton nmr and CD spectra of gramicidin S (GS) [cyclic-(Val1,1''-Orn2,2''-Leu3,3''-D-Phe4,4''-Pro5,5'')2 and of GS analogs.sbd.namely, [D-Ala4,4'']-GS, [Gly-4,4'']-GS, and [L-Ala4,4'']-GS.sbd.were analyzed. The molecular conformation of [D-Ala4,4'']-GS is similar to that of GS, with the trans form about the D-Ala-Pro peptide bond. The molecular conformation of [Gly4,4'']-GS depends on the solvent compositon of dimethylsulfoxide-d6/trifluoroethanol (DMSO-d6/TFE) and DMSO-d6/H2O as well as the solute concentration. In DMSO-d6 solution, [Gly4,4'']-GS forms the GS-type conformation of the monomer at lower concentration. At higher concentration, the GS-type conformer is converted to the other one that forms molecular aggregates. The cis form about the X-Pro peptide bonds is found for [Gly4,4'']-GS and [L-Ala4,4'']-GS in DMSO-d6 and for [L-Ala4,4'']-GS in TFE solution. The large temperature dependences of .alpha.-proton chemical shifts of [L-Ala4,4'']-GS in DMSO-d6 solution indicate that the confomer equilibrium changes with temperature. The GS-type conformation is not formed in [L-Ala4,4'']-GS. The two active peptide analogs, [D-Ala4,4'']-GS and [Gly4,4'']-GS, interact with the phospholipid membrane, taking the GS-type conformation. By contrast, an inactive analog, [L-Ala4,4'']-GS, does not interact with phospholipid membrane. The activities of GS analogs are found to correlate to the formation of the GS-type conformation upon binding with phospholipid membrane.