신명철 (경상대학교)

한빛사논문

조회144

경상대학교

CV File 463 kb

J. Control. Release, Available online 2 July 2024 | https://doi.org/10.1016/j.jconrel.2024.06.061 Genetically engineered long-acting Esculentin-2CHa(1-30) fusion protein with potential applicability for the treatment of NAFLD

Jaewoong Lee ^a,1, Reeju Amatya ^b,1, Kyung Eun Kim ^a, Young-Hoon Park^c, Eunmi Hong ^c, Krismala Djayanti ^d, Kyoung Ah Min ^d, Gu Seob Roh ^a, Meong Cheol Shin ^b

^aDepartment of Anatomy and Convergence Medical Science, Metabolic Dysfunction Liver Disease Research Center, Institute of Medical Science, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, Republic of Korea

^bCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, 501 Jinju Daero, Jinju, Gyeongnam 52828, Republic of Korea

^cNew Drug Development Center, Daegu, Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu 41061, Republic of Korea

^dCollege of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, Gimhae, Gyeongnam 50834, Republic of Korea

¹Jaewoong Lee^† and Reeju Amatya^† contributed equally to the manuscript.

Correspondence to: Gu Seob Roh, Meong Cheol Shin

Abstract

Esculentin-2CHa(1-30) (‟ESC") has been reported as a potent anti-diabetic peptide with little toxicity. However, its very short plasma residence time severely limits the therapeutic efficacy. To address this issue, we genetically engineered a fusion protein of tandem trimeric ESC with an albumin binding domain (ABD) and a fusion partner, SUMO (named ‟SUMO-3 × ESC-ABD"). The SUMO-3 × ESC-ABD, successfully produced from E. coli, showed low cellular and hemolytic toxicity while displaying potent activities for the amelioration of hyperglycemia as well as non-alcoholic fatty liver disease (NAFLD) in vitro. In animal studies, the estimated plasma half-life of SUMO-3 × ESC-ABD was markedly longer (427-fold) than that of the ESC peptide. In virtue of the extended plasma residence, the SUMO-3 × ESC-ABD could produce significant anti-hyperglycemic effects that lasted for >2 days, while both the ESC or ESC-ABD peptides elicited little effects. Further, twice-weekly treatment for 10 weeks, the SUMO-3 × ESC-ABD displayed significant improvement in blood glucose control with a reduction in body weight. Most importantly, a significant improvement in the conditions of NAFLD was observed in the SUMO-3 × ESC-ABD-treated mice. Along the systemic effects (by improved glucose tolerance and body weight reduction), direct inhibition of the hepatocyte lipid uptake was suggested as the major mechanism of the anti-NAFLD effects. Overall, this study demonstrated the utility of the long-acting SUMO-3 × ESC-ABD as a potent drug candidate for the treatment of NAFLD.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-07-03)
연구진국내 연구진
분야 의약학 > 약리의학

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