함정엽 (한국과학기술연구원(KIST))

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조회255

한국과학기술연구원(KIST)

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Adv. Healthc. Mater., Feb 29 2024, | https://doi.org/10.1002/adhm.202303480 Peptide-Drug Conjugate with Statistically Designed Transcellular Peptide for Psoriasis-Like Inflammation

Do Hyun Bae ^1,2‡, Hayeon Bae ^3,4‡, Hyung-Seok Yu ⁵, Banzrach Dorsembe ^5,6, Young Hyun No ^3,4, Taejung Kim ^5,6, Nam Hyeong Kim ^3,4, Jinwoo Kim ⁵, Jiyool Kim ^5,6, Bok-Soo Lee ³, Ye Ji Kim ^2,3,4, Seongchan Park ^3,4, Zinah Hilal Khaleel ^2,3,4, Deok Hyang Sa ^3,4, Eui-Chul Lee ^3,4, Jaecheol Lee ^7,8,9,10, Jungyeob Ham ^5,6*, Jin-Chul Kim^5,6*, Yong Ho Kim ^{1,2,3,4,9,11*}

¹Department of Biomedical Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.

²Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Suwon, 16419, Republic of Korea.

³SKKU Advanced Institute of Nano Technology (SAINT), Suwon, 16419, Republic of Korea.

⁴Department of Nano Science and Technology, Sungkyunkwan University, Suwon, 16419, Republic of Korea.

⁵Natural Products Research Institute, Korea Institute of Science and Technology (KIST), Gangneung, 25451, Republic of Korea.

⁶KIST school, University of Science and Technology (UST), Seoul, 02792, Republic of Korea.

⁷Sungkyunkwan University, Suwon, 16419, Republic of Korea.

⁸Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon, 16419, Republic of Korea.

⁹Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon, 16419, Republic of Korea.

¹⁰IMNEWRUN Inc, Suwon, 16419, Republic of Korea.

¹¹Department of Nano Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.

^‡Equally contributing authors

^*CORRESPONDING AUTHORS: Jungyeob Ham, Jin-Chul Kim, Yong Ho Kim

Abstract

Peptide-drug conjugates (PDCs) are a promising class of drug delivery systems that utilize covalently conjugated carrier peptides with therapeutic agents. PDCs offer several advantages over traditional drug delivery systems, including enhanced target engagement, improved bioavailability, and increased cell permeability. However, the development of efficient transcellular peptides capable of effectively transporting drugs across biological barriers remains an unmet need. In this study, we employ physicochemical criteria based on cell penetrating peptides (CPPs) to design transcellular peptides derived from an antimicrobial peptides (AMPs) library. Among those the statistically designed transcellular peptides (SDTs), SDT7 exhibits higher skin permeability, faster kinetics, and improved cell permeability in human keratinocyte cells compared to the control peptide. Subsequently, we find that 6-Paradol (PAR) exhibited inhibitory activity against phosphodiesterase 4 (PDE4), which can be utilized for an anti-inflammatory PDC. The transcellular PDC (SDT7-conjugated with PAR, named as TM5) is evaluated in mouse models of psoriasis, exhibiting superior therapeutic efficacy compared to PAR alone. These findings highlight the potential of transcellular peptide-drug conjugates (TDCs) as a promising approach for the treatment of inflammatory skin disorders. This article is protected by copyright. All rights reserved.

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형식Research article
게재일2024년 02월 (BRIC 등록일 2024-03-04)
연구진국내 연구진
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