한빛사논문
- 조회680
Sejong Choia,1, Yeeun Leeb,1, Jeongin Hwanga, Dahyun Chuna, Heebeom Koob, Yan Leea
aDepartment of Chemistry, Seoul National University, Seoul 08826, Republic of Korea
bDepartment of Medical Life Sciences and Department of Bio-medicine & Health Sciences, The Catholic University of Korea, Seoul 06591, Republic of Korea
1These authors contributed equally to this work.
Corresponding authors: Heebeom Koo, Yan Lee
Abstract
In this study, we propose a self-cleaving protein that responds to acidic pH, pH inteinN150, as a pH-responsive linker for the selective delivery of protein-based drugs. Being stable at neutral and degradable at weakly acidic pH, pH inteinN150 can be obtained by mutating key amino acids of pH intein, thus stimulating self-cleavage. Unlike chemical linkers, which require additional conjugation steps, protein linkers can be incorporated into protein pharmaceuticals during protein expression. As proof-of-concepts, intracellular penetration of proteins can be selectively turned on or off by cleaving pH inteinN150 near the cell-penetrating peptide sequence at weakly acidic pH. Furthermore, the apoptosis-inducing activity of human tumor necrosis factor-related apoptosis-inducing ligand (hTRAIL) can be selectively activated by cleaving pH inteinN150 adjacent to the albumin binding domain (ABD) at weakly acidic pH. Thus, we expect that this new protein linker can be used for actively controlling various protein-based drugs responding to delicate pH variations around inflammatory or cancerous tissues. These findings have been revealed in an in vivo tumor xenograft mouse model showing elongated systemic circulation and selective induction of tumor toxicity by ABD-pH inteinN150-hTRAIL.
논문정보
- Research article
- 2023년 02월 (BRIC 등록일 2023-01-09)
- 국내 연구진
- 바이오·의료융합 > 바이오소재
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