The Impact of Tyrosine Iodination on the Aggregation and Cleavage Kinetics of MMP-9-Responsive Peptide Sequences.
The Impact of Tyrosine Iodination on the Aggregation and Cleavage Kinetics of MMP-9-Responsive Peptide Sequences.
复制标题
酪氨酸碘化对MMP-9反应性肽序列的聚集和裂解动力学的影响。
DOI：
10.1021/acsbiomaterials.1c01488
复制
发表时间：
2022-02-14
影响因子：
5.8
通讯作者：
Ulijn, Rein, V
中科院分区：
文献类型：
--
作者：
MacPherson, Douglas S.;McPhee, Scott A.;Zeglis, Brian M.;Ulijn, Rein, V
关键词：
基质金属蛋白酶（MMP）在一些转移性癌症中过度表达，在这些癌症中它们负责细胞外基质的降解和重塑。近年来，基质金属蛋白酶已经成为酶响应性诊断探针的有前途的目标，因为寡肽可以被设计为通过暴露于这些酶而选择性水解。最终目标是开发放射性碘化肽作为用于核成像和治疗的MMP敏感工具的超分子构建块，我们设计了三种含有酪氨酸或碘酪氨酸的MMP-9响应肽，以评估碘酪氨酸引入对肽结构和裂解动力学的影响。我们发现，含有碘酪氨酸的肽进行更迅速，更完全的水解MMP-9。虽然所研究的肽主要是无序的，但发现碘化增加了芳香残基驱动的肽聚集的程度。我们确定，这些碘化相关的趋势源于通过H-和卤素键合改善的整体分子内秩序，除了由于卤代酪氨酸引入的空间和静电效应的自组装肽的分子间组织。这些基本观察为开发用于局部放射性碘基肿瘤成像的酶触发肽聚集工具提供了见解。
Matrix metalloproteinase (MMP) enzymes are over-expressed by some metastatic cancers, in which they are responsible for the degradation and remodeling of the extracellular matrix. In recent years, MMPs have emerged as promising targets for enzyme-responsive diagnostic probes because oligopeptides can be designed to be selectively hydrolyzed by exposure to these enzymes. With the ultimate goal of developing radio-iodinated peptides as supramolecular building blocks for MMP-sensitive tools for nuclear imaging and therapy, we designed three MMP-9-responsive peptides containing either tyrosine or iodotyrosine, in order to assess the impact of iodotyrosine introduction to peptide structure and cleavage kinetics. We found that the peptides containing iodotyrosine underwent more rapid and more complete hydrolysis by MMP-9. While the peptides under investigation were predominantly disordered, it was found that iodination increased the degree of aromatic residue-driven aggregation of the peptides. We determined that these iodination-related trends stem from improved overall intramolecular order through H- and halogen bonding, in addition to intermolecular organization of the self-assembled peptides due to steric and electrostatic effects introduced by the halogenated tyrosine. These fundamental observations provide insights for the development of enzyme-triggered peptide aggregation tools for localized radioactive iodine- based tumor imaging.
登录
查看更多内容
影响因子：
4.1
作者：
Cobb, Jared S.;Zai-Rose, Valeria;Janorkar, Amol, V
通讯作者：
Janorkar, Amol, V
影响因子：
21.8
作者：
Frederix, Pim W. J. M.;Scott, Gary G.;Tuttle, Tell
通讯作者：
Tuttle, Tell
影响因子：
14.8
作者：
Greenfield, Norma J.
通讯作者：
Greenfield, Norma J.
具有 MMP-2 响应性的短肽水凝胶的合理设计用于受控抗癌肽递送
影响因子：
6.2
作者：
Chen, Cuixia;Zhang, Yu;Xu, Hai
通讯作者：
Xu, Hai
DOI：
10.1016/0926-6585(65)90009-9
发表时间：
1965-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
COWGILL, RW
通讯作者：
COWGILL, RW