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Updated: Feb 16, 2026

Construction of Cyclic Cell-Penetrating Peptides for Enhanced Penetration of Biological Barriers
Published on: September 19, 2022
Enhanced intracellular peptide delivery by multivalent cell-penetrating peptide with bioreducible linkage
Hyungjin Kim1, Mizuki Kitamatsu2, Takashi Ohtsuki1
1Department of Medical Bioengineering, Okayama University, 3-1-1 Tsushimanaka, Okayama 700-8530, Japan.
Abstract:
Multivalent cell-penetrating peptides (CPPs) have been reported to show enhancement in cellular uptake and endosomolytic activity. However, its application was limited to trans-delivery of cargo which is lower in cellular uptake efficiency of cargo than cis-delivery. Here, we tried the cis-delivery of cargo with multivalent CPP by preparing bioreducible dimeric CPP-cargo with apoptotic activity using TatBim peptide, a fusion of Tat CPP and Bim peptide derived from Bim apoptosis-inducing protein. Dimeric TatBim was almost twice as highly internalized by cells and significantly induced apoptosis compared to monomeric TatBim. Contribution of bioreducible linkage of dimeric TatBim towards apoptotic activity was also confirmed.
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