Control of self-assembling oligopeptide matrix formation through systematic variation of amino acid sequence
Control of self-assembling oligopeptide matrix formation through systematic variation of amino acid sequence
复制标题
DOI：
10.1016/s0142-9612(01)00099-0
复制
发表时间：
2002-01-01
期刊：
影响因子：
14
通讯作者：
Lauffenburger, DA
中科院分区：
文献类型：
--
作者：
Caplan, MR;Schwartzfarb, EM;Lauffenburger, DA
为了阐明由自组装寡肽原位转化而成的生物相容性材料的设计原理，我们研究了一类能够在盐溶液中自组装形成三维基质的寡肽。这类多肽。拥有重复的氨基酸残基序列，类型为：hydrophobic/negatively-charged/hydrophobic/positively-charged.我们系统地改变了这种序列类型的三个主要方面：(1)疏水侧链：(2)带电侧链，(3)重复数。用流变法判断基质的形成，确定了驱动从粘性状态向凝胶态转变所需的盐溶液的临界浓度。我们发现，侧链疏水性的增加降低了临界盐浓度，这与我们之前对DLVO理论的验证一致，该理论解释了这种自组装现象。(生物大分子1(2000)627)。此外，我们发现，增加重复次数会产生一种双相依赖关系--先降低，然后增加，临界盐浓度。我们认为，这一结果可能是由于随着多肽长度的增加，更大的疏水(有利)效应和更大的熵(不利)效应之间的不平等竞争。最后，我们发现，我们可以利用这种理解来合理地改变带电的侧链，以产生一个自组装的寡肽序列，该序列在pH值为7时在没有盐的情况下保持粘性，但在生理盐浓度存在的情况下保持凝胶，这是一个非常有用的技术应用性质。(C)2001爱思唯尔科学有限公司。保留所有权利。
In order to elucidate design principles for biocompatible materials that can be created by in situ transformation from self assembling oligopeptides, we investigate a class of oligopeptides that can self-assemble in salt solutions to form three-dimensional matrices. This class of peptides. possesses a repeated sequence of amino acid residues with the type: hydrophobic/negatively-charged/hydrophobic/positively-charged. We systematically vary three chief aspects of this sequence type: (1) the hydrophobic side chains: (2) the charged side-chains, and (3) the number of repeats. Employing a rheometric assay to judge matrix formation, we determine the critical concentration of NaCl salt solution required to drive transformation from viscous state to gel state. We find that increasing side-chain hydrophobicity decreases the critical salt concentration in accord with our previous validation of DLVO theory for explaining this self-assembly phenomenon Caplan et al. (Biomacromolecules 1 (2000) 627). Further, we find that increasing the number of repeats yields a biphasic dependence-first decreasing, then increasing, the critical salt concentration. We believe that this result is likely due to an unequal competition between a greater hydrophobic (favorable) effect and a greater entropic (unfavorable) effect as the peptide length is increased. Finally, we find that we can use this understanding to rationally alter the charged side-chains to create a self-assembling oligopeptide sequence that at pH 7 remains viscous in the absence of salt but gels in the presence of physiological salt concentrations, a highly useful property for technological applications. (C) 2001 Elsevier Science Ltd. All rights reserved.