Close mimicry of lung surfactant protein B by "clicked" dimers of helical, cationic peptoids.
Close mimicry of lung surfactant protein B by "clicked" dimers of helical, cationic peptoids.
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DOI：
10.1002/bip.21309
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发表时间：
2009
期刊：
影响因子：
2.9
通讯作者：
Barron, Annelise E.
中科院分区：
文献类型：
--
作者：
Dohm, Michelle T.;Seurynck-Servoss, Shannon L.;Seo, Jiwon;Zuckermann, Ronald N.;Barron, Annelise E.
关键词：
提出了一类模拟SP-B的类肽二聚体，其中两个两亲性阳离子螺旋通过非手性八聚体链连接在一起。SP-B是肺表面活性物质替代治疗中重要的治疗蛋白，但其大规模分离或化学合成是不现实的。先前已尝试通过二硫键介导的SP-B1-25和其他多肽模拟物的二聚来增强SP-B的二硫键结构的生物仿生，这相对于单体提高了表面活性。在这里，描述了二硫键或‘点击’介导的(1，3-偶极环加成)二聚反应以及连接物化学对类肽单体的脂类相关表面活性的影响。结果表明，在表面平衡和脉动气泡表面计量学研究中，与二硫键和单体对应的DPPC：POPG：PA脂膜相比，‘点击’的类肽二聚体在体外增强了脂膜的表面活性。在脉动气泡表面测定仪上，含有“点击”的类肽二聚体的膜的吸附表面张力为22mN m−1，最大和最小循环值分别为42mN m−1和接近零，表现优于所有已有的类肽单体和二聚体以及两个SP-B衍生肽。
A family of peptoid dimers developed to mimic SP-B is presented, where two amphipathic, cationic helices are linked by an achiral octameric chain. SP-B is a vital therapeutic protein in lung surfactant replacement therapy, but its large-scale isolation or chemical synthesis is impractical. Enhanced biomimicry of SP-B’s disulfide-bonded structure has been previously attempted via disulfide-mediated dimerization of SP-B1-25 and other peptide mimics, which improved surface activity relative to the monomers. Herein, the effects of disulfide- or ‘click’-mediated (1,3-dipolar cycloaddition) dimerization, as well as linker chemistry, on the lipid-associated surfactant activity of a peptoid monomer are described. Results revealed that the ‘clicked’ peptoid dimer enhanced in vitro surface activity in a DPPC:POPG:PA lipid film relative to its disulfide-bonded and monomeric counterparts in both surface balance and pulsating bubble surfactometry studies. On the pulsating bubble surfactometer, the film containing the ‘clicked’ peptoid dimer outperformed all presented peptoid monomers and dimers, and two SP-B derived peptides, attaining an adsorbed surface tension of 22 mN m−1, and maximum and minimum cycling values of 42 mN m−1 and near-zero, respectively.
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影响因子：
3.2
作者：
Holub, JM;Jang, HJ;Kirshenbaum, K
通讯作者：
Kirshenbaum, K
DOI：
10.1073/pnas.95.8.4309
发表时间：
1998-04-14
影响因子：
11.1
作者：
Armand, P;Kirshenbaum, K;Bradley, EK
通讯作者：
Bradley, EK
影响因子：
2.9
作者：
Booth, V;Waring, AJ;Keough, KMW
通讯作者：
Keough, KMW
DOI：
10.1073/pnas.88.16.7451
发表时间：
1991-08-01
影响因子：
11.1
作者：
BRUNI, R;TAEUSCH, HW;WARING, AJ
通讯作者：
WARING, AJ
DOI：
10.1164/ajrccm.153.1.8542150
发表时间：
1996-01-01
影响因子：
24.7
作者：
Cochrane, CG;Revak, SD;Alberts, MS
通讯作者：
Alberts, MS