title: Efficient Mini-Transporter for Cytosolic Protein Delivery.
abstract: An efficient method to deliver active proteins into cytosol is highly desirable to advance protein-based therapeutics. Arginine-rich cell-penetrating peptides (RPPs) have been intensively studied for intracellular protein delivery, and their applications require further improvement on delivery efficiency, serum stability, and cytotoxicity. Designing synthetic analogs of RPPs provides an alternative way to achieve efficient cytosolic protein delivery. Herein we report the design and synthesis of a dendritic small molecule TG6, which is composed of one rigid planar core and four flexible arms with one guanidinium on each arm. Protein structure and function are well preserved in the TG6-protein conjugates, which are readily internalized into cytosol. Our study demonstrates that TG6 is a serum-stable and low-toxic molecular transporter delivering both small cargoes and large active proteins efficiently into cytosol.
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), Department of Chemistry, University of Science and Technology of China , Hefei, Anhui 230026, P. R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), Department of Chemistry, University of Science and Technology of China , Hefei, Anhui 230026, P. R. China.
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Yan
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), Department of Chemistry, University of Science and Technology of China , Hefei, Anhui 230026, P. R. China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhao
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), Department of Chemistry, University of Science and Technology of China , Hefei, Anhui 230026, P. R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), Department of Chemistry, University of Science and Technology of China , Hefei, Anhui 230026, P. R. China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Ma
mesh_terms: D001120:Arginine; D057846:Cell-Penetrating Peptides; D003600:Cytosol; D016503:Drug Delivery Systems; D019791:Guanidine; D026901:Membrane Transport Proteins
chemical_list: D057846:Cell-Penetrating Peptides; D026901:Membrane Transport Proteins; D001120:Arginine; D019791:Guanidine
keywords: cell penetrating peptides; cytosolic delivery; guanidinium; protein delivery; structure design