期刊
BIOCONJUGATE CHEMISTRY
卷 32, 期 5, 页码 958-963出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.bioconjchem.1c00108
关键词
-
类别
资金
- ERC Advanced Grant [Artisym 694120]
- Dutch Ministry of Education, Culture and Science [024.001.035]
Protein cages show promise as carrier systems in nanomedicine due to their defined size and biodegradability, but require stability and surface modifications for drug delivery. By combining protein engineering and bio-orthogonal chemistry, successful introduction of functional peptides and fluorescent dyes into CCMV capsids for cell uptake studies was achieved.
Protein cages hold much promise as carrier systems in nanomedicine, due to their well-defined size, cargo-loading capacity, and inherent biodegradability. In order to make them suitable for drug delivery, they have to be stable under physiological conditions. In addition, often surface modifications are required, for example, to improve cell targeting or reduce the particle immunogenicity by PEGylation. For this purpose, we investigated the functionalization capacity of the capsid of cowpea chlorotic mottle virus (CCMV), modified at the interior with a stabilizing elastinlike polypeptide (ELP) tag, by employing a combination of protein engineering and bio-orthogonal chemistry. We first demonstrated the accessibility of the native cysteine residue in ELP-CCMV as a site-selective surface-exposed functional handle, which was not available in the native CCMV capsid. An additional bio-orthogonal functional handle was introduced by incorporation of the noncanonical amino acid, azido-phenylalanine (AzF), using the amber suppression mechanism. Dual site-selective presentation of both a cell-penetrating TAT peptide and a fluorophore to track the particles was demonstrated successfully in HeLa cell uptake studies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据