Rational design of MMP degradable peptide-based supramolecular filaments.
Rational design of MMP degradable peptide-based supramolecular filaments.
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DOI：
10.1021/bm500020j
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发表时间：
2014-04-14
影响因子：
6.2
通讯作者：
Cui, Honggang
中科院分区：
文献类型：
--
作者：
Lin, Yi-An;Ou, Yu-Chuan;Cheetham, Andrew G.;Cui, Honggang
通过小分子肽的自组装形成的一维纳米结构已经被广泛探索用作各种生物医学背景中的生物材料。然而，与可以被设计为可被感兴趣的酶/蛋白酶特异性降解的单个肽不同，它们的自组装纳米结构，特别是富含β-折叠的那些，通常对酶促降解具有抗性，因为特异性切割位点通常嵌入纳米结构内部。我们在这里报告的合理设计的β-折叠丰富的超分子细丝，可以特异性地解离成不太稳定的胶束组装体和单体后，处理与基质金属蛋白酶-2（MMP-2）。通过连接的寡脯氨酸段的淀粉样蛋白衍生的肽序列，我们首先合成了一个两亲性肽，可以经历一个快速的形态转变，响应pH值的变化。然后，我们使用MMP-2特异性肽底物作为多价交联剂，在pH 4.5下将淀粉样蛋白样细丝共价固定在自组装状态。我们的研究结果表明，交联的细丝在pH 7.5下是稳定的，但在MMP-2裂解肽交联剂后逐渐分解成短得多的细丝。我们相信，报告的工作提出了一个新的设计平台，为创建淀粉样蛋白超分子丝响应酶降解。
One-dimensional nanostructures formed by self-assembly of small molecule peptides have been extensively explored for use as biomaterials in various biomedical contexts. However, unlike individual peptides that can be designed to be specifically degradable by enzymes/proteases of interest, their self-assembled nanostructures, particularly those rich in β-sheets, are generally resistant to enzymatic degradation because the specific cleavage sites are often embedded inside the nanostructures. We report here on the rational design of β-sheet rich supramolecular filaments that can specifically dissociate into less stable micellar assemblies and monomers upon treatment with matrix metalloproteases-2 (MMP-2). Through linkage of an oligoproline segment to an amyloid-derived peptide sequence, we first synthesized an amphiphilic peptide that can undergo a rapid morphological transition in response to pH variations. We then used MMP-2 specific peptide substrates as multivalent cross-linkers to covalently fix the amyloid-like filaments in the self-assembled state at pH 4.5. Our results show that the cross-linked filaments are stable at pH 7.5 but gradually break down into much shorter filaments upon cleavage of the peptidic cross-linkers by MMP-2. We believe that the reported work presents a new design platform for the creation of amyloid-like supramolecular filaments responsive to enzymatic degradation.
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DOI：
10.1021/la401025r
发表时间：
2013-06-04
期刊：
Langmuir : the ACS journal of surfaces and colloids
影响因子：
--
作者：
Dehsorkhi A;Hamley IW;Seitsonen J;Ruokolainen J
通讯作者：
Ruokolainen J
影响因子：
7.015
作者：
Lin YA;Ou YC;Cheetham AG;Cui H
通讯作者：
Cui H
影响因子：
15
作者：
Cheetham, Andrew G.;Zhang, Pengcheng;Lin, Yi-an;Lock, Lye Lin;Cui, Honggang
通讯作者：
Cui, Honggang
影响因子：
5.5
作者：
Cui, Honggang;Chen, Zhiyun;Pochan, Darrin J.
通讯作者：
Pochan, Darrin J.
影响因子：
15
作者：
Arora, PS;Ansari, AZ;Dervan, PB
通讯作者：
Dervan, PB