pH as a trigger of peptide β-sheet self-assembly and reversible switching between nematic and isotropic phases
pH as a trigger of peptide β-sheet self-assembly and reversible switching between nematic and isotropic phases
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DOI：
10.1021/ja021047i
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发表时间：
2003-08-13
影响因子：
15
通讯作者：
Boden, N
中科院分区：
文献类型：
--
作者：
Aggeli, A;Bell, M;Boden, N
合理设计的合成肽分层自组装成β片带、带状、原纤维和纤维，为水凝胶、有机凝胶或液晶等软固体材料开辟了潜在的有用途径。这里展示了Glu （-CH2CH2COOH）或Orn （-CH2CH2CH2NH2）如何结合到11个氨基酸肽的初级结构中，通过简单地改变ph值，可以快速（秒）可逆地控制自组装。单体肽溶液通常在浓度超过0.003 v/v时，可以在几秒钟内切换到例如由相互连接的定向有序原纤维阵列组成的向列凝胶状态，反之也可以。这是与冻干肽溶解途径相比较的向列流体和凝胶，这是不切实际的长，需要许多小时甚至几天。首先证明了一个重要的设计原则，即纤维分散体的稳定需要每个肽分子具有一个单位的净正电荷或负电荷，然后用于设计11个氨基酸的肽P-11-3 (ch3co - gln - gln - arg - phe - gln - trp - gln - phe - gln - gln - gln - gln - nh2)，其自组装行为不依赖于pH （1 < pH < 10）。然后通过适当定位Glu或Orn侧链来控制pH，从而使带状亚结构中肽-肽相互作用的自由能分别受到Glu（-）中的γ - coo -或Orn（+）中的δ - nh3 +之间的直接静电力的强烈影响。两种多肽的行为说明了这一设计原理：P-11-4 （ch3co - gln - gln - arg - pheu - glu - trp - gln - gln - nh2）可以通过增加pH值从向列向转变为各向同性流体状态，P-11-5 （ch3co - gln - gln - orn - pheh - orn - trp - orn - pheh - gln - gln - gln - gln - gln - gln - gln - gln - gln - gln - gln - gln - gln - gln - gln - gln - nh2）则表现出相反的行为。纤维分散体的酸碱滴定显示，Glu的γ - cooh或Orn（+）的6-NH3+的去质子化发生在高达5个pH单位的宽波段，这是聚电解质的一个特征。因此，控制自组装的能量参数值可以随着ph的变化而平稳而连续地变化。这使得通过相对少量的酸或碱的添加，通常是1 / 10(3)体积的1 M HCl或NaOH，就可以触发各向同性流体到向列相的转变。
The hierarchical self-assembly of rationally designed synthetic peptides into beta-sheet tapes, ribbons, fibrils, and fibers opens up potentially useful routes to soft-solidlike materials such as hydrogels, organogels, or liquid crystals. Here, it is shown how incorporation of Glu (-CH2CH2COOH) or Orn (-CH2CH2CH2NH2) into the primary structure of an 11 amino acid peptide enables self-assembly to be rapidly (seconds) and reversibly controlled by simply changing pH. Solutions of monomeric peptide, typically at concentrations in excess of 0.003 v/v, can be switched within seconds to, for example, nematic gel states comprised of interconnected orientationally ordered arrays of fibrils or vice versa. This is to be compared with the lyophilized peptide dissolution route to nematic fluids and gels which is impracticably long, taking many hours or even days. An important design principle, that stabilization of fibrillar dispersions requires of the order of one unit of net positive or negative charge per peptide molecule, is first demonstrated and then used to design an 11 amino acid peptide P-11-3 (CH3CO-Gln-Gln-Arg-Phe-Gln-Trp-Gln-Phe-Gln-Gln-Gln-NH2) whose self-assembly behavior is independent of pH (1 < pH < 10). pH control is then incorporated by appropriately positioning Glu or Orn side chains so that the peptide-peptide free energy of interaction in the tapelike substructure is strongly influenced by direct electrostatic forces between gamma-COO- in Glu(-) or delta-NH3+ in Orn(+), respectively. This design principle is illustrated by the behavior of two peptides: P-11-4 (CH3CO-Gln-Gln-Arg-Phe-Glu-Trp-Glu-Phe-Glu-Gln-Gln-NH2) which can be switched from its nematic to its isotropic fluid state by increasing pH and P-11-5 (CH3CO-Gln-Gln-Orn-Phe-Orn-Trp-Orn-Phe-Gln-Gln-Gln-NH2) designed to exhibit the converse behavior. Acid-base titrations of fibrillar dispersions reveal deprotonation of the gamma-COOH of Glu or of the 6-NH3+ of Orn(+) occurs over wide bands of up to 5 pH units, a feature of polyelectrolytes. The values of the energy parameters controlling self-assembly can therefore be smoothly and continuously varied by changing pH. This enables isotropic fluid-to-nematic transitions to be triggered by relatively small additions of acid or base, typically 1 part in 10(3) by volume of 1 M HCl or NaOH.