황현석 (연세대학교)

한빛사논문

조회277

황현석Hyun-seok Hwang

연세대학교

J. Control. Release, Volume 366, February 2024, Pages 104-113 | https://doi.org/10.1016/j.jconrel.2023.12.028 Inhibition of protein-protein interactions using biodegradable depsipeptide nanoassemblies

Se-Hwan Choi ^a,1, Hyun-seok Hwang ^a,1, Seongryeong Han^b,1, Hohyeon Eom ^c, Jun Shik Choi ^a,d, Sanghun Han ^a, Donghyun Lee ^b, Soo Yeon Lee ^c, Heebeom Koo ^b, Ho Jeong Kwon ^c, Yong-beom Lim^a

^aDepartment of Materials Science and Engineering, Yonsei University, Seoul, Republic of Korea

^bDepartment of Medical Life Sciences, Department of Biomedicine & Health Sciences, Catholic Photomedicine Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

^cChemical Genomics Leader Research Laboratory, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea

^dLaboratory of Tissue Engineering, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea

¹These authors contributed equally to this work.

Corresponding authors : Heebeom Koo, Ho Jeong Kwon, Yong-beom Lim

Abstract

Although peptides notoriously have poor intrinsic pharmacokinetic properties, it is well-known that nanostructures with excellent pharmacokinetic properties can be designed. Noticing that peptide inhibitors are generally nonpolar, here, we consolidate the peptide inhibitor targeting intracellular protein-protein interactions (PPIs) as an integral part of biodegradable self-assembled depsipeptide nanostructures (SdPNs). Because the peptide inhibitor has the dual role of PPI inhibition and self-assembly in this design, problems associated with the poor pharmacokinetics of peptides and encapsulation/entrapment processes can be overcome. Optimized SdPNs displayed better tumor targeting and PPI inhibition properties than the comparable small molecule inhibitor in vivo. Kinetics of PPI inhibition for SdPNs were gradual and controllable in contrast to the rapid inhibition kinetics of the small molecule. Because SdPN is modular, any appropriate peptide inhibitor can be incorporated into the platform without concern for the poor pharmacokinetic properties of the peptide.

논문정보

형식Research article
게재일2024년 02월 (BRIC 등록일 2024-01-03)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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