The antiviral peptide carbobenzoxy-D-phenylalanyl-L-phenylalanylglycine changes the average conformation of phospholipids in membranes.
The antiviral peptide carbobenzoxy-D-phenylalanyl-L-phenylalanylglycine changes the average conformation of phospholipids in membranes.
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抗病毒肽苯甲氧酯-D-苯丙氨酰-L-苯丙氨酰甘氨酸改变膜中磷脂的平均构象。
DOI：
10.1021/bi00096a032
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发表时间：
1993
期刊：
影响因子：
2.9
通讯作者：
Watts,A
中科院分区：
文献类型：
--
作者：
Yeagle,PL;Dentino,AR;Smith,FT;Spooner,P;Watts,A
摘要：用多核固体核磁共振（NMR）研究了抗病毒肽苄氧羰基-D-苯丙氨酰-L-苯丙氨酰甘氨酸（ZfFG）对磷脂酰胆碱在水合双层中平均构象的影响。磷脂酰胆碱在胆碱N-甲基、胆碱的α和β位、酰基链的C2碳和磷脂酰胆碱的酰基链的所有碳中被特异性地氘代（单独地）。磷脂酰胆碱也是用甘油和富含13 C的烃链之间的酯键的羰基碳合成的。在酰基链中全氘代的磷脂酰胆碱的21 H NMR显示在ZfFG存在下具有最大四极分裂的氘的强度损失，而粉末图案的其余部分基本上不受影响。在C2碳（代表CD键产生最大的四极分裂）处特异性氘代的磷脂酰胆碱显示出相同的强度损失，这表明甘油附近的磷脂构象和构象动力学发生了变化。对在羰基碳中用13 C标记的磷脂酰胆碱的13 C NMR光谱中的粉末图案的分析揭示了由于ZfFG的存在而导致的sn-1羰基的平均取向的显著变化，而sn-2羰基取向没有变化。在theheadgroup构象的变化，作为检测到的氘在α和α-亚甲基的胆碱头基和31 P NMR的磷酸盐部分，反映了ZfFG的羧基与磷脂酰胆碱双层的相互作用的静电性质。胆碱的N-甲基中的氘没有观察到显着影响。从这些数据可以得出结论，磷脂酰胆碱在双层中的分子的甘油片段周围具有一种以上的构象。在不存在ZfFG的情况下，两个羰基在它们的取向上是不等价的。抗病毒肽ZfFG有利于构象中的两个酯羰基（相对于旋转扩散轴）的平均取向大致相等。这种改变的磷脂构象可能是在抗病毒化合物存在下观察到的磷脂堆积差异的来源。表观2 H NMR强度的损失可能是由于在ZfFG存在下磷脂酰胆碱所采用的（至少）两种构象之间的交换动力学（在10 - 5** s的时间尺度上）。
Revised Manuscript Received September 3, 1993* abstract: The influence of the antiviral peptide, carbobenzoxy-D-phenylalanyl-L-phenylalanylglycine (ZfFG), on the average conformation of phosphatidylcholine in hydrated bilayers was investigated with multinuclear solid state magnetic resonance(NMR). Phosphatidylcholine was specifically deuterated (separately) in the choline TV-methyls, the a and ß positions of the choline, the C2 carbon of the acyl chains, and at all the carbons of the acyl chains of the phosphatidylcholine. Phosphatidylcholine was also synthesized with the carbonyl carbons of the ester bonds between the glycerol and the hydrocarbon chains enriched in 13C. 2* H NMR of the phosphatidylcholine perdeuterated in the acyl chains showed a loss of intensity from the deuteriums with the largest quadrupole splitting in the presence of ZfFG, while the remainder of the powder pattern was largely unaffected. The phosphatidylcholine specifically deuteratedat the C2 carbon (representative of the CD bonds giving rise to the largest quadrupole splittings) showed the same loss of intensity suggesting changes in the phospholipid conformation and conformational dynamics near the glycerol. Analysis of the powder patterns in the 13C NMR spectrum of phosphatidylcholine labeled with 13C in the carbonyl carbons revealed a significant change in the average orientation of the sn-1 carbonyl due to the presence of the ZfFG and no change in the sn-2 carbonyl orientation. Changes in theheadgroup conformation, as detected by 2H NMR of the deuteriums in the a and ß methylenes of the choline headgroup and 31P NMR of the phosphate segment, reflected the electrostatic nature of the interaction of the carboxyl of ZfFG with phosphatidylcholine bilayers. No significant effect was observed from the deuteriums in the TV-methyls of the choline. From these data it was concluded that phosphatidylcholine had access to more than one conformation around the glycerol segment of the molecule in a bilayer. In the absence of ZfFG, the two carbonyls are inequivalent in their orientation. The antiviral peptide ZfFG favored a conformation in which the average orientations of the two ester carbonyls (with respect to the axis of rotation diffusion) were approximately equivalent. This altered phospholipid conformation may be the source of the differences in phospholipid packing observed in the presence of the antiviral compound. The loss of apparent 2H NMR intensity was likely due to the dynamics (on the time scale of 10~ 5** s) of the interchange between the (at least) two conformations adopted by the phosphatidylcholine in the presence of ZfFG.