Biophysical mimicry of lung surfactant protein B by random nylon-3 copolymers.
Biophysical mimicry of lung surfactant protein B by random nylon-3 copolymers.
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DOI：
10.1021/ja909734n
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发表时间：
2010-06-16
影响因子：
15
通讯作者：
Barron, Annelise E.
中科院分区：
文献类型：
--
作者：
Dohm, Michelle T.;Mowery, Brendan P.;Czyzewski, Ann M.;Stahl, Shannon S.;Gellman, Samuel H.;Barron, Annelise E.
非天然寡聚体最近显示出作为肺表面活性蛋白B和C（SP-B和SP-C）的功能类似物的前景，肺表面活性蛋白是两种螺旋和两亲性蛋白，其对于正常呼吸至关重要。SP-B和SP-C的非天然模拟物的产生以前被限制为逐步的、序列特异性的合成，这导致旨在表现特定结构属性的离散寡聚体。在这里，我们提出了一种替代的方法SP-B模拟，是基于序列随机共聚物含有阳离子和亲脂性亚基。这些材料是尼龙-3家族的成员，通过β-内酰胺的开环聚合制备。最好的尼龙-3聚合物在混合脂质膜中显示出有前途的体外表面活性剂活性。脉动气泡表面测定法的数据表明，含有最表面活性的聚合物的膜达到吸附和动态循环性能，超过那些离散的肽拟模仿SP-B。通过SP-C中发现的翻译后修饰，将N-末端十八烷酰基单元连接到尼龙-3共聚物上，通过降低表面积压缩百分比以达到较低的最小表面张力，提供了进一步的改进。相对于SP-B衍生肽和基于类肽的模拟物，共聚物的细胞毒性作用减弱。目前的研究提供的证据表明，序列无规共聚物可以模拟肺表面活性蛋白在混合脂质膜中的体外表面活性行为。这些发现提高了无规共聚物可能用于开发肺表面活性剂替代物的可能性，这是一个有吸引力的前景，因为这种聚合物比序列特异性低聚物更容易制备。
Non-natural oligomers have recently shown promise as functional analogues of lung surfactant proteins B and C (SP-B and SP-C), two helical and amphiphilic proteins that are critical for normal respiration. The generation of non-natural mimics of SP-B and SP-C has previously been restricted to step-by-step, sequence-specific synthesis, which results in discrete oligomers that are intended to manifest specific structural attributes. Here we present an alternative approach to SP-B mimicry that is based on sequence-random copolymers containing cationic and lipophilic subunits. These materials, members of the nylon-3 family, are prepared by ring-opening polymerization of β-lactams. The best of the nylon-3 polymers display promising in vitro surfactant activities in a mixed lipid film. Pulsating bubble surfactometry data indicate that films containing the most surface-active polymers attain adsorptive and dynamic-cycling properties that surpass those of discrete peptides intended to mimic SP-B. Attachment of an N-terminal octadecanoyl unit to the nylon-3 copolymers – inspired by the post-translational modifications found in SP-C – affords further improvements by reducing the percent surface area compression to reach low minimum surface tension. Cytotoxic effects of the copolymers are diminished relative to that of an SP-B-derived peptide and a peptoid-based mimic. The current study provides evidence that sequence-random copolymers can mimic the in vitro surface-active behavior of lung surfactant proteins in a mixed lipid film. These findings raise the possibility that random copolymers might be useful for developing a lung surfactant replacement, which is an attractive prospect given that such polymers are easier to prepare than are sequence-specific oligomers.
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影响因子：
15
作者：
Appella, DH;Christianson, LA;Gellman, SH
通讯作者：
Gellman, SH
DOI：
10.1164/ajrccm.154.2.8756826
发表时间：
1996-08-01
影响因子：
24.7
作者：
Hawgood, S;Ogawa, A;Benson, B
通讯作者：
Benson, B
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
影响因子：
4.8
作者：
Beck, DC;Ikegami, M;Weaver, TE
通讯作者：
Weaver, TE
影响因子：
4.7
作者：
Chu-Kung, AF;Bozzelli, KN;Tirrell, MV
通讯作者：
Tirrell, MV