Interaction of gramicidin S and its aromatic amino-acid analog with phospholipid membranes
Interaction of gramicidin S and its aromatic amino-acid analog with phospholipid membranes
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DOI：
10.1529/biophysj.108.137471
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发表时间：
2008-10-01
影响因子：
3.4
通讯作者：
Wheaton, Laura
中科院分区：
文献类型：
--
作者：
Jelokhani-Niaraki, Masoud;Hodges, Robert S.;Wheaton, Laura
为了研究短杆菌肽 S 样抗菌肽与生物膜的相互作用机制，一系列五种十聚环状阳离子 β-折叠-β-转角肽与所有可能的芳香族 D-氨基酸组合，Cyclo(Val-Lys-Leu-D-Ar1-Pro-Val-Lys-Leu-D-Ar2-Pro) (Ar Phe、Tyr、 Trp），被合成。这些环肽的构象在水溶液和脂质囊泡中是相当的。等温滴定量热法测量揭示了环肽与 POPC 和 POPE/POPG 脂囊泡的熵驱动结合。肽与两种囊泡系统的结合都是吸热的，但含有 Trp-Trp 和 Tyr-Trp 对的肽与 POPC 囊泡的结合是放热的。将一位点和两位点结合（分配）模型分别应用于放热和吸热结合过程的结合等温线，从而确定了肽-脂质膜结合常数（K-b）。吸热两步结合过程的 K-b1 和 K-b2 值对应于高和低结合亲和力 (K-b1 >= 100 K-b2)。使用肽构建体之一中酪氨酸-色氨酸对之间的荧光共振能量转移来估计环肽从缓冲液转移到脂质双层表面时的构象变化。环肽构象在脂质双层表面吸附后扩展，并与外部单层更深入地相互作用，导致双层变形，这可能导致非特异性瞬时肽-脂质孔状区域的形成，导致膜裂解。
To investigate the mechanism of interaction of gramicidin S-like antimicrobial peptides with biological membranes, a series of five decameric cyclic cationic beta-sheet-beta-turn peptides with all possible combinations of aromatic D-amino acids, Cyclo(Val-Lys-Leu-D-Ar1-Pro-Val-Lys-Leu-D-Ar2-Pro) (Ar Phe, Tyr, Trp), were synthesized. Conformations of these cyclic peptides were comparable in aqueous solutions and lipid vesicles. Isothermal titration calorimetry measurements revealed entropy-driven binding of cyclic peptides to POPC and POPE/POPG lipid vesicles. Binding of peptides to both vesicle systems was endothermic-exceptions were peptides containing the Trp-Trp and Tyr-Trp pairs with exothermic binding to POPC vesicles. Application of one-and two-site binding (partitioning) models to binding isotherms of exothermic and endothermic binding processes, respectively, resulted in determination of peptide-lipid membrane binding constants (K-b). The K-b1 and K-b2 values for endothermic two-step binding processes corresponded to high and low binding affinities (K-b1 >= 100 K-b2). Conformational change of cyclic peptides in transferring from buffer to lipid bilayer surfaces was estimated using fluorescence resonance energy transfer between the Tyr-Trp pair in one of the peptide constructs. The cyclic peptide conformation expands upon adsorption on lipid bilayer surface and interacts more deeply with the outer monolayer causing bilayer deformation, which may lead to formation of nonspecific transient peptide-lipid porelike zones causing membrane lysis.