Olmedo Ivonne, Araya Eyleen, Sanz Fausto, Medina Elias, Arbiol Jordi, Toledo Pedro, Alvarez-Lueje Alejandro, Giralt Ernest, Kogan Marcelo J
Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Olivos 1007, Chile.
Bioconjug Chem. 2008 Jun;19(6):1154-63. doi: 10.1021/bc800016y. Epub 2008 May 30.
In a previous work, we studied the interaction of beta-amyloid fibrils (Abeta) with gold nanoparticles (AuNP) conjugated with the peptide CLPFFD-NH2. Here, we studied the effect of changing the residue sequence of the peptide CLPFFD-NH2 on the efficiency of conjugation to AuNP, the stability of the conjugates, and the affinity of the conjugates to the Abeta fibrils. We conjugated the AuNP with CLPFFD-NH 2 isomeric peptides (CDLPFF-NH2 and CLPDFF-NH2) and characterized the resulting conjugates with different techniques including UV-Vis, TEM, EELS, XPS, analysis of amino acids, agarose gel electrophoresis, and CD. In addition, we determined the proportion of AuNP bonded to the Abeta fibrils by ICP-MS. AuNP-CLPFFD-NH2 was the most stable of the conjugates and presented more affinity for Abeta fibrils with respect to the other conjugates and bare AuNP. These findings help to better understand the way peptide sequences affect conjugation and stability of AuNP and their interaction with Abeta fibrils. The peptide sequence, the steric effects, and the charge and disposition of hydrophilic and hydrophobic residues are crucial parameters when considering the design of AuNP peptide conjugates for biomedical applications.
在之前的一项工作中，我们研究了β-淀粉样蛋白纤维（Abeta）与缀合有肽CLPFFD-NH2的金纳米颗粒（AuNP）之间的相互作用。在此，我们研究了改变肽CLPFFD-NH2的残基序列对其与AuNP缀合效率、缀合物稳定性以及缀合物与Abeta纤维亲和力的影响。我们将AuNP与CLPFFD-NH2的同分异构肽（CDLPFF-NH2和CLPDFF-NH2）进行缀合，并用包括紫外可见光谱、透射电子显微镜、电子能量损失谱、X射线光电子能谱、氨基酸分析、琼脂糖凝胶电泳和圆二色光谱等不同技术对所得缀合物进行表征。此外，我们通过电感耦合等离子体质谱法测定了与Abeta纤维结合的AuNP的比例。AuNP-CLPFFD-NH2是最稳定的缀合物，相对于其他缀合物和裸AuNP，它对Abeta纤维表现出更高的亲和力。这些发现有助于更好地理解肽序列如何影响AuNP的缀合和稳定性以及它们与Abeta纤维的相互作用。在考虑用于生物医学应用的AuNP肽缀合物的设计时，肽序列、空间效应以及亲水和疏水残基的电荷和分布是关键参数。
