Effects of peptide secondary structure on the interaction with oppositely charged microgels.
Effects of peptide secondary structure on the interaction with oppositely charged microgels.
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肽二级结构对与带相反电荷的微凝胶相互作用的影响。
DOI：
10.1021/bm101165e
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发表时间：
2011
影响因子：
6.2
通讯作者：
M. Malmsten
中科院分区：
文献类型：
--
作者：
Ronja Månsson;H. Bysell;P. Hansson;A. Schmidtchen;M. Malmsten
以EFKRIVQRIKDFLRNLV （EFK17）为研究对象，研究了肽二级结构对抗菌肽与不同电荷密度的反电荷聚丙烯酸-共丙烯酰胺微凝胶相互作用的影响。通过d -对映体(EFK17-d/a； E(dF)KR(dI)VQR（dI)KD(dF)LRNLV）或色氨酸（EFK17-W/a； EWKRWVQRWKDFLRNLV）取代，可以精确控制该肽的构象依赖性和非构象依赖性两亲性。通过圆二色性研究了肽的二级结构，通过微操纵仪辅助光和荧光显微镜研究了微凝胶对肽结合和释放的反应，并通过溶液耗尽测量测定了微凝胶中的肽摄取。结果表明，肽与微凝胶的结合受到肽二级结构的高度影响。EFK17-a具有一个理想的螺旋结构，所有极性/带电氨基酸位于螺旋的一侧，所有非极性/疏水残基位于另一侧，对肽与微凝胶的结合表现出明显的α-螺旋诱导作用。另一方面，EFK17-d/a没有这种两亲性螺旋诱导。与此相呼应的是，EFK17-a比EFK17-d/a与微凝胶的结合程度要高得多，并且肽诱导的微凝胶溶胀也要大得多。对于EFK17-W/a，证明了构象依赖性和非构象依赖性的两亲性效应。总的来说，结果表明，肽构象方面需要考虑肽/微凝胶相互作用，例如，在多肽药物的微凝胶载体系统的设计中。
The importance of peptide secondary structure on the interaction between antimicrobial peptides and oppositely charged poly(acrylic acid-co-acrylamide) microgels of various charge density was investigated for EFKRIVQRIKDFLRNLV (EFK17). Through D-enantiomer (EFK17-d/a; E(dF)KR(dI)VQR(dI)KD(dF)LRNLV) or tryptophan (EFK17-W/a; EWKRWVQRWKDFLRNLV) substitutions, both conformation-dependent and -independent amphiphilicity of this peptide could be precisely controlled. Peptide secondary structure was investigated by circular dichroism, whereas microgel deswelling and reswelling in response to peptide binding and release were studied by micromanipulator-assisted light and fluorescence microscopy, and peptide uptake in the microgels was determined from solution depletion measurements. Results show that peptide binding to the microgel is highly influenced by peptide secondary structure. EFK17-a, characterized by an idealized helix with all polar/charged amino acids located at one side of the helix, and all nonpolar/hydrophobic residues on the other, displays pronounced α-helix induction on peptide binding to the microgels. EFK17-d/a, on the other hand, displays no such amphiphilic helix induction. Mirroring this, EFK17-a displays substantially higher binding to the microgels than EFK17-d/a as well as much larger peptide-induced microgel deswelling. For EFK17-W/a, both conformation-dependent and -independent amphiphilicity effects were demonstrated. Overall, the results show that peptide conformational aspects need to be considered in peptide/microgel interactions, for example, in the design of microgel carrier systems for peptide drugs.