An Amphiphilic Sulfonatocalix[5]arene as an Activator for Membrane Transport of Lysine-rich Peptides and Proteins

Pan, YC (Pan, Yu-Chen)^{[ 1 ]} ; Barba-Bon, A (Barba-Bon, Andrea)^{[ 2 ]} ; Tian, HW (Tian, Han-Wen)^{[ 1 ]} ; Ding, F (Ding, Fei)^{[ 1 ]} ; Hennig, A (Hennig, Andreas)^{[ 2,3,4,5 ]} ; Nau, WM (Nau, Werner M.)^{[ 2 ]} ; Guo, DS (Guo, Dong-Sheng)^{[ 1 ]}

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2020, DOI: 10.1002/anie.202011185

摘要

Lysine (K) is an important target residue for protein and peptide delivery across membranes. K is the most frequently exposed residue in proteins, leading to high demand for the development of K-compatible transport activators. However, designing activators for K-rich peptides and proteins is more challenging than for arginine-rich species because of the kosmotropic nature of K and its recognition difficulty. In this study, we designed a new amphiphilic sulfonatocalix[5]arene (sCx5-6C) as a K-compatible transport activator. sCx5-6C was tailored with two key elements, recognition of K and the ability to embed into membranes. We measured the membrane transport efficiencies of alpha-poly-l-lysine, heptalysine, and histones across artificial membranes and of alpha-poly-l-lysine into live cells, activated by sCx5-6C. The results demonstrate that sCx5-6C acts as an efficient activator for translocating K-rich peptides and proteins, which cannot be achieved by known arginine-compatible activators.