Engineering complementary hydrophobic interactions to control β-hairpin peptide self-assembly, network branching, and hydrogel properties.
Engineering complementary hydrophobic interactions to control β-hairpin peptide self-assembly, network branching, and hydrogel properties.
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DOI：
10.1021/bm500874t
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发表时间：
2014-11-10
影响因子：
6.2
通讯作者：
Pochan DJ
中科院分区：
文献类型：
--
作者：
Sathaye S;Zhang H;Sonmez C;Schneider JP;MacDermaid CM;Von Bargen CD;Saven JG;Pochan DJ
MAX1MAX1VKVKVK-β-发夹多肽(VKVKVKVPT-KVKVKVKV-NH2)已被证明形成具有两个折叠的多肽形成的横截面的纳米纤维，形成一个疏水的富含缬氨酸的核心，并且聚合的纤维主要表现为β-SHAP氢键。这些纳米纤维通过纤维缠绕和纤维分支形成水凝胶网络。MAX1水凝胶网络中的纤维分支提供了在外加剪切应力下流动的能力，并在剪切停止时立即重塑水凝胶固体。新的β-发夹被设计来限制纳米纤维生长过程中的分支，因为组装的纤维疏水核心具有空间专一性。用侧链体积大得多和小得多的2-萘丙氨酸(NAL)和丙氨酸(A)残基取代MAX1的非转位氨基酸，得到LNK1(NAL)K(NAL)KAKAK-VDPPT-KAKAK(NAL)K(NAL)-NH2。LNK1的目标是与疏水核心中特定的“锁和钥匙”互补堆积自结合，以适应NaL和Ala残基侧链。实验观察到的LNK1多肽中纤维分支减少的表现是剪切后缺乏固体水凝胶形成，这与MAX1分支纤维系统形成了鲜明的对比。分子动力学模拟提供了组件内多肽间相互作用的分子图像，这与MAX1对LNK1的分支倾向一致，并与实验观察一致。
The MAX1 β-hairpin peptide (VKVKVKVK-VDPPT-KVKVKVKV-NH2) has been shown to form nanofibrils having a cross-section of two folded peptides forming a hydrophobic, valine-rich core, and the polymerized fibril exhibits primarily β-sheet hydrogen bonding. These nanofibrils form hydrogel networks through fibril entanglements as well as fibril branching. Fibrillar branching in MAX1 hydrogel networks provide the ability to flow under applied shear stress and immediately reform a hydrogel solid on cessation of shear. New β-hairpins were designed to limit branching during nanofibril growth because of steric specificity in the assembled fibril hydrophobic core. The nonturn valines of MAX1 were substituted by 2-naphthylalanine (Nal) and alanine (A) residues, with much larger and smaller side chain volumes, respectively, to obtain LNK1 (Nal)K(Nal)KAKAK-VDPPT-KAKAK(Nal)K(Nal)-NH2. LNK1 was targeted to self-associate with a specific “lock and key” complementary packing in the hydrophobic core in order to accommodate the Nal and Ala residue side chains. The experimentally observable manifestation of reduced fibrillar branching in the LNK1 peptide is the lack of solid hydrogel formation after shear in stark contrast to the MAX1 branched fibril system. Molecular dynamics simulations provide a molecular picture of interpeptide interactions within the assembly that is consistent with the branching propensity of MAX1 vs LNK1 and in agreement with experimental observations.
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影响因子：
41.2
作者：
通讯作者：
--
DOI：
10.1002/anie.201006652
发表时间：
2011-02-11
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Micklitsch CM;Knerr PJ;Branco MC;Nagarkar R;Pochan DJ;Schneider JP
通讯作者：
Schneider JP
影响因子：
5.6
作者：
Calhoun, JR;Kono, H;Saven, JG
通讯作者：
Saven, JG
DOI：
10.1073/pnas.1112595109
发表时间：
2012-05-08
影响因子：
11.1
作者：
Lanci, Christopher J.;MacDermaid, Christopher M.;Saven, Jeffery G.
通讯作者：
Saven, Jeffery G.
影响因子：
3.4
作者：
Leonard, Sarah R.;Cormier, Ashley R.;Paravastu, Anant K.
通讯作者：
Paravastu, Anant K.