Novel Arginine-containing Macrocyclic MMP Inhibitors: Synthesis, 99mTc-labeling, and Evaluation

Abstract Matrix metalloproteinases (MMPs) are involved in tissue remodeling. Accordingly, MMP inhibitors and related radiolabeled analogs are important tools for MMP-targeted imaging and therapy in a number of diseases. Herein, we report design, synthesis, and evaluation of a new Arginine-containing...

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Autores principales:	Yunpeng Ye, Jakub Toczek, Kiran Gona, Hye-Yeong Kim, Jinah Han, Mahmoud Razavian, Reza Golestani, Jiasheng Zhang, Terence L. Wu, Mousumi Ghosh, Jae-Joon Jung, Mehran M. Sadeghi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1e49a26ed93a4eedbdffd93fc7f56c2c
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spelling	oai:doaj.org-article:1e49a26ed93a4eedbdffd93fc7f56c2c2021-12-02T15:08:04ZNovel Arginine-containing Macrocyclic MMP Inhibitors: Synthesis, 99mTc-labeling, and Evaluation10.1038/s41598-018-29941-22045-2322https://doaj.org/article/1e49a26ed93a4eedbdffd93fc7f56c2c2018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-29941-2https://doaj.org/toc/2045-2322Abstract Matrix metalloproteinases (MMPs) are involved in tissue remodeling. Accordingly, MMP inhibitors and related radiolabeled analogs are important tools for MMP-targeted imaging and therapy in a number of diseases. Herein, we report design, synthesis, and evaluation of a new Arginine-containing macrocyclic hydroxamate analog, RYM, its hydrazinonicotinamide conjugate, RYM1 and 99mTc-labeled analog 99mTc-RYM1 for molecular imaging. RYM exhibited potent inhibition against a panel of recombinant human (rh) MMPs in vitro. RYM1 was efficiently labeled with 99mTcO4 − to give 99mTc-RYM1 in a high radiochemical yield and high radiochemical purity. RYM1 and its decayed labeling product displayed similar inhibition potencies against rhMMP-12. Furthermore, 99mTc-RYM1 exhibited specific binding with lung tissue from lung-specific interleukin-13 transgenic mice, in which MMP activity is increased in conjunction with tissue remodeling and inflammation. The results support further development of such new water-soluble Arginine-containing macrocyclic hydroxamate MMP inhibitors for targeted imaging and therapy.Yunpeng YeJakub ToczekKiran GonaHye-Yeong KimJinah HanMahmoud RazavianReza GolestaniJiasheng ZhangTerence L. WuMousumi GhoshJae-Joon JungMehran M. SadeghiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yunpeng Ye Jakub Toczek Kiran Gona Hye-Yeong Kim Jinah Han Mahmoud Razavian Reza Golestani Jiasheng Zhang Terence L. Wu Mousumi Ghosh Jae-Joon Jung Mehran M. Sadeghi Novel Arginine-containing Macrocyclic MMP Inhibitors: Synthesis, 99mTc-labeling, and Evaluation
description	Abstract Matrix metalloproteinases (MMPs) are involved in tissue remodeling. Accordingly, MMP inhibitors and related radiolabeled analogs are important tools for MMP-targeted imaging and therapy in a number of diseases. Herein, we report design, synthesis, and evaluation of a new Arginine-containing macrocyclic hydroxamate analog, RYM, its hydrazinonicotinamide conjugate, RYM1 and 99mTc-labeled analog 99mTc-RYM1 for molecular imaging. RYM exhibited potent inhibition against a panel of recombinant human (rh) MMPs in vitro. RYM1 was efficiently labeled with 99mTcO4 − to give 99mTc-RYM1 in a high radiochemical yield and high radiochemical purity. RYM1 and its decayed labeling product displayed similar inhibition potencies against rhMMP-12. Furthermore, 99mTc-RYM1 exhibited specific binding with lung tissue from lung-specific interleukin-13 transgenic mice, in which MMP activity is increased in conjunction with tissue remodeling and inflammation. The results support further development of such new water-soluble Arginine-containing macrocyclic hydroxamate MMP inhibitors for targeted imaging and therapy.
format	article
author	Yunpeng Ye Jakub Toczek Kiran Gona Hye-Yeong Kim Jinah Han Mahmoud Razavian Reza Golestani Jiasheng Zhang Terence L. Wu Mousumi Ghosh Jae-Joon Jung Mehran M. Sadeghi
author_facet	Yunpeng Ye Jakub Toczek Kiran Gona Hye-Yeong Kim Jinah Han Mahmoud Razavian Reza Golestani Jiasheng Zhang Terence L. Wu Mousumi Ghosh Jae-Joon Jung Mehran M. Sadeghi
author_sort	Yunpeng Ye
title	Novel Arginine-containing Macrocyclic MMP Inhibitors: Synthesis, 99mTc-labeling, and Evaluation
title_short	Novel Arginine-containing Macrocyclic MMP Inhibitors: Synthesis, 99mTc-labeling, and Evaluation
title_full	Novel Arginine-containing Macrocyclic MMP Inhibitors: Synthesis, 99mTc-labeling, and Evaluation
title_fullStr	Novel Arginine-containing Macrocyclic MMP Inhibitors: Synthesis, 99mTc-labeling, and Evaluation
title_full_unstemmed	Novel Arginine-containing Macrocyclic MMP Inhibitors: Synthesis, 99mTc-labeling, and Evaluation
title_sort	novel arginine-containing macrocyclic mmp inhibitors: synthesis, 99mtc-labeling, and evaluation
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/1e49a26ed93a4eedbdffd93fc7f56c2c
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Novel Arginine-containing Macrocyclic MMP Inhibitors: Synthesis, 99mTc-labeling, and Evaluation

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