American Chemical Society
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Amphiphilic α‑Peptoid-deoxynojirimycin Conjugate-based Multivalent Glycosidase Inhibitor for Hypoglycemic Effect and Fluorescence Imaging

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posted on 2024-03-20, 06:04 authored by Guang-Yuan Wang, Dong-Xiao Yan, Rui-Xue Rong, Bing-Ye Shi, Gao-Juan Lin, Fangqian Yin, Wen-Tong Wei, Xiao-Liu Li, Ke-Rang Wang
Multivalent glycosidase inhibitors based on 1-deoxynojirimycin derivatives against α-glucosidases have been rapidly developed. Nonetheless, the mechanism based on self-assembled multivalent glucosidase inhibitors in living systems needs to be further studied. It remains to be determined whether the self-assembly possesses sufficient stability to endure transit through the small intestine and subsequently bind to the glycosidases located therein. In this paper, two amphiphilic compounds, 1-deoxynojirimycin and α-peptoid conjugates (LP-4DNJ-3C and LP-4DNJ-6C), were designed. Their self-assembling behaviors, multivalent α-glucosidase inhibition effect, and fluorescence imaging on living organs were studied. LP-4DNJ-6C exhibited better multivalent α-glucosidase inhibition activities in vitro. Moreover, the self-assembly of LP-4DNJ-6C could effectively form a complex with Nile red. The complex showed fluorescence quenching effect upon binding with α-glucosidases and exhibited potent fluorescence imaging in the small intestine. This result suggests that a multivalent hypoglycemic effect achieved through self-assembly in the intestine is a viable approach, enabling the rational design of multivalent hypoglycemic drugs.