Dephosphorylation of D-peptide derivatives to form biofunctional, supramolecular nanofibers/hydrogels and their potential applications for intracellular imaging and intratumoral chemotherapy.

Dephosphorylation of D-peptide derivatives to form biofunctional, supramolecular nanofibers/hydrogels and their potential applications for intracellular imaging and intratumoral chemotherapy.
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D肽衍生物的去磷酸化形成生物功能,超分子纳米纤维/水凝胶及其在细胞内成像和肿瘤内化疗的潜在应用。

DOI:
10.1021/ja404215g
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发表时间:
2013-07-03
影响因子:
15
通讯作者:
Xu, Bing
Xu, Bing
中科院分区:
化学1区
文献类型:
--
作者:
Li, Jiayang;Gao, Yuan;Kuang, Yi;Shi, Junfeng;Du, Xuewen;Zhou, Jie;Wang, Huaimin;Yang, Zhimou;Xu, Bing

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D-肽作为天然存在的L-肽的对映体,通常抵抗内源性蛋白酶,并且可能对大多数酶不敏感。但目前还不清楚磷酸酶是否或如何催化D-肽的去磷酸化。在这项工作中,我们研究了通过酶促去磷酸化的D-肽的纳米纤维的形成。通过比较L-肽和D-肽水凝胶因子的酶促水凝胶化,我们发现水凝胶因子前体的手性对从酪氨酸磷酸残基上去除磷酸基团所导致的酶促水凝胶化的影响很小。治疗剂(例如,紫杉醇)或荧光团(例如,4-硝基-2,1,3-苯并恶二唑(NBD))与基于D-肽的水凝胶因子的结合提供了一种新型的生物稳定或生物相容的水凝胶因子,其可分别在肿瘤内化疗或细胞内成像中找到应用。这项工作,作为第一个全面和系统的研究意想不到的酶去磷酸化的D-肽,说明了一个有用的方法来产生超分子水凝胶,具有生物稳定性和其他所需的功能。
D-peptides, as the enantiomers of the naturally occurring L-peptides, usually resist endogenous proteases and presumably insensitive to most enzymes. But it is unclear whether or how a phosphatase catalyzes the dephosphorylation from D-peptides. In this work, we examine the formation of the nanofibers of D-peptides via enzymatic dephosphorylation. By comparing the enzymatic hydrogelation of L-peptide and D-peptide based hydrogelators, we find that the chirality of the precursors of the hydrogelators affects little on the enzymatic hydrogelation resulted from the removal of phosphate group from a tyrosine phosphate residue. The attachment of a therapeutic agent (e.g., taxol) or a fluorophore (e.g., 4-nitro-2,1,3-benzoxadiazole (NBD)) to the D-peptide based hydrogelators afford a new type of biostable or biocompatible hydrogelators, which may find applications in intratumoral chemotherapy or intracellular imaging, respectively. This work, as the first comprehensive and systematic study of the unexpected enzymatic dephosphorylation of D-peptides, illustrates a useful approach to generate supramolecular hydrogels that have both biostability and other desired functions.
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