Multivalent glucosidase inhibitors based on perylene bisimide and iminosugar conjugates

Yang, Jian-Xing; Li, Juanjuan; Yin, Fang-Qian; Wang, Guangyuan; Wei, Wen-Tong; Li, Xiaoliu; Wang, Ke-Rang

doi:10.1016/j.ejmech.2022.114621

Cited by 6 publications

(4 citation statements)

References 30 publications

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“…Preparation of α-Glucosidase from Mice. 35,52 α-Glucosidase was extracted from a C57BL/6J mice model. (6−8 weeks old, male) C57BL/6J mice with free access of water were fasted for 24 h. They were then euthanized by cervical dislocation.…”

Section: Dls and Tem Assaymentioning

confidence: 99%

“…The hypoglycemic activities in mice were related to the total hydrogen bond energy 34 and the binding strength between the inhibitors and the α-glucosidases. 35 These findings offer valuable insights for the future design of multivalent drugs targeting hypoglycemia. 36 However, future investigation is needed to confirm whether the self-assemblies retain sufficient stability to reach and bind to glycosidases in the small intestine.…”

Section: Introductionmentioning

confidence: 99%

“…Since 2019, multivalent glycosidase inhibitors based on self-assembling 1-deoxynojirimycin derivatives , targeting α-glucosidases were developed; these inhibitors demonstrate good α-glucosidase inhibition activities in vitro and potent hypoglycemic effects in vivo . The hypoglycemic activities in mice were related to the total hydrogen bond energy and the binding strength between the inhibitors and the α-glucosidases . These findings offer valuable insights for the future design of multivalent drugs targeting hypoglycemia .…”

Section: Introductionmentioning

confidence: 99%

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

Wang,

Yan,

Rong

et al. 2024

J. Med. Chem.

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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.

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Section: Dls and Tem Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Wang,

Yan,

Rong

et al. 2024

J. Med. Chem.

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“…The construction of multivalent iminosugars follows conventional strategies, including modifications and protecting group chemistry of the iminosugars [ 50 , 61 , 62 ], coupling reactions using click chemistry [ 45 , 48 , 63 ], and recently developed supramolecular self-assembly based on π–π stacking or hydrophobic interactions [ 64 , 65 , 66 ]. Multimerization of the pyrrolidines using these strategies resulted in some interesting results.…”

Section: Introductionmentioning

confidence: 99%

Multivalent Pyrrolidine Iminosugars: Synthesis and Biological Relevance

et al. 2022

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Recently, the strategy of multivalency has been widely employed to design glycosidase inhibitors, as glycomimetic clusters often induce marked enzyme inhibition relative to monovalent analogs. Polyhydroxylated pyrrolidines, one of the most studied classes of iminosugars, are an attractive moiety due to their potent and specific inhibition of glycosidases and glycosyltransferases, which are associated with many crucial biological processes. The development of multivalent pyrrolidine derivatives as glycosidase inhibitors has resulted in several promising compounds that stand out. Herein, we comprehensively summarized the different synthetic approaches to the preparation of multivalent pyrrolidine clusters, from total synthesis of divalent iminosugars to complex architectures bearing twelve pyrrolidine motifs. Enzyme inhibitory properties and multivalent effects of these synthesized iminosugars were further discussed, especially for some less studied therapeutically relevant enzymes. We envision that this comprehensive review will help extend the applications of multivalent pyrrolidine iminosugars in future studies.

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Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2021–2022

Harvey

2024

Mass Spectrometry Reviews

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The use of matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry for the analysis of carbohydrates and glycoconjugates is a well‐established technique and this review is the 12th update of the original article published in 1999 and brings coverage of the literature to the end of 2022. As with previous review, this review also includes a few papers that describe methods appropriate to analysis by MALDI, such as sample preparation, even though the ionization method is not MALDI. The review follows the same format as previous reviews. It is divided into three sections: (1) general aspects such as theory of the MALDI process, matrices, derivatization, MALDI imaging, fragmentation, quantification and the use of computer software for structural identification. (2) Applications to various structural types such as oligo‐ and polysaccharides, glycoproteins, glycolipids, glycosides and biopharmaceuticals, and (3) other general areas such as medicine, industrial processes, natural products and glycan synthesis where MALDI is extensively used. Much of the material relating to applications is presented in tabular form. MALDI is still an ideal technique for carbohydrate analysis, particularly in its ability to produce single ions from each analyte and advancements in the technique and range of applications show little sign of diminishing.

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Multivalent glucosidase inhibitors based on perylene bisimide and iminosugar conjugates

Cited by 6 publications

References 30 publications

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

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

Multivalent Pyrrolidine Iminosugars: Synthesis and Biological Relevance

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2021–2022

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