Issue 40, 2023

Catalytic olefin metathesis in blood

Abstract

The direct synthesis of drugs in vivo enables drugs to treat diseases without causing side effects in healthy tissues. Transition-metal reactions have been widely explored for uncaging and synthesizing bioactive drugs in biological environments because of their remarkable reactivity. Nonetheless, it is difficult to develop a promising method to achieve in vivo drug synthesis because blood cells and metabolites deactivate transition-metal catalysts. We report that a robust albumin-based artificial metalloenzyme (ArM) with a low loading (1–5 mol%) can promote Ru-based olefin metathesis to synthesize molecular scaffolds and an antitumor drug in blood. The ArM retained its activity after soaking in blood for 24 h and provided the first example of catalytic olefin cross metathesis in blood. Furthermore, the cyclic-Arg-Gly-Asp (cRGD) peptide-functionalized ArM at lower dosages could still efficiently perform in vivo drug synthesis to inhibit the growth of implanted tumors in mice. Such a system can potentially construct therapeutic drugs in vivo for therapies without side effects.

Graphical abstract: Catalytic olefin metathesis in blood

Supplementary files

Article information

Article type
Edge Article
Submitted
22 jul 2023
Accepted
05 sep 2023
First published
27 sep 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2023,14, 11033-11039

Catalytic olefin metathesis in blood

I. Nasibullin, H. Yoshioka, A. Mukaimine, A. Nakamura, Y. Kusakari, T. Chang and K. Tanaka, Chem. Sci., 2023, 14, 11033 DOI: 10.1039/D3SC03785A

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