首页> 外文期刊>Advanced Functional Materials >Glycine N-Methylation in NGR-Tagged Nanocarriers Prevents Isoaspartate Formation and Integrin Binding without Impairing CD13 Recognition and Tumor Homing
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Glycine N-Methylation in NGR-Tagged Nanocarriers Prevents Isoaspartate Formation and Integrin Binding without Impairing CD13 Recognition and Tumor Homing

机译:NGR标记的纳米载体中的甘氨酸N-甲基化可在不损害CD13识别和肿瘤归巢的情况下防止异麦草酸盐形成和整联蛋白结合。

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摘要

NGR (asparagine-glycine-arginine) is a tumor vasculature-homing peptide motif widely used for the functionalization of drugs, nanomaterials, and imaging compounds for cancer treatment and diagnosis. Unfortunately, this motif has a strong propensity to undergo rapid deamidation. This reaction, which converts NGR into isoDGR, is associated with receptor switching from CD13 to integrins, with potentially important manufacturing and pharmacological and toxicological implications. It is found that glycine N-methylation of NGR-tagged nanocarriers completely prevents asparagine deamidation without impairing CD13 recognition. Studies in animal models have shown that the methylated NGR motif can be exploited for delivering radiolabeled compounds and nanocarriers, such as tumor necrosis factor-a-bearing nanogold and liposomal doxorubicin, to tumors with improved selectivity. These findings suggest that this NGR derivative is a stable and efficient tumor-homing ligand that can be used for delivering functional nanomaterials to tumor vasculature.
机译:NGR(天冬酰胺-甘氨酸-精氨酸)是一种肿瘤血管归巢肽基序,广泛用于药物,纳米材料和成像化合物的功能化,以治疗和诊断癌症。不幸的是,该图案很容易进行快速脱酰胺。该反应将NGR转化为isoDGR,与受体从CD13转变为整联蛋白有关,具有潜在的重要制造,药理和毒理学意义。发现NGR标记的纳米载体的甘氨酸N-甲基化完全防止了天冬酰胺脱酰胺而不损害CD13的识别。动物模型研究表明,可以利用甲基化的NGR基序将放射性标记的化合物和纳米载体(例如,携带肿瘤坏死因子-α的纳米金和脂质体阿霉素)以提高的选择性传递给肿瘤。这些发现表明该NGR衍生物是稳定且有效的肿瘤归巢配体,其可用于将功能性纳米材料递送至肿瘤脉管系统。

著录项

  • 来源
    《Advanced Functional Materials》 |2017年第36期|1701245.1-1701245.10|共10页
  • 作者单位

    IRCCS San Raffaele Sci Inst, Via Olgettina 58, I-20132 Milan, Italy|Univ Vita Salute San Raffaele, I-20132 Milan, Italy;

    IRCCS San Raffaele Sci Inst, Via Olgettina 58, I-20132 Milan, Italy;

    IRCCS San Raffaele Sci Inst, Via Olgettina 58, I-20132 Milan, Italy;

    IRCCS San Raffaele Sci Inst, Via Olgettina 58, I-20132 Milan, Italy;

    IRCCS San Raffaele Sci Inst, Via Olgettina 58, I-20132 Milan, Italy;

    IRCCS San Raffaele Sci Inst, Via Olgettina 58, I-20132 Milan, Italy;

    IRCCS San Raffaele Sci Inst, Via Olgettina 58, I-20132 Milan, Italy;

    IRCCS San Raffaele Sci Inst, Via Olgettina 58, I-20132 Milan, Italy;

    CNR, Ist Chim Riconoscimento Mol, Via Mario Bianco 9, I-20131 Milan, Italy;

    IRCCS San Raffaele Sci Inst, Via Olgettina 58, I-20132 Milan, Italy|Univ Milano Bicocca, Dept Med & Surg, Via Cadore 48, I-20900 Monza, Italy;

    IRCCS San Raffaele Sci Inst, Via Olgettina 58, I-20132 Milan, Italy|Univ Milano Bicocca, Dept Med & Surg, Via Cadore 48, I-20900 Monza, Italy;

    Ist Giannina Gaslini, Via G Gaslini 5, I-16148 Genoa, Italy;

    Ist Giannina Gaslini, Via G Gaslini 5, I-16148 Genoa, Italy;

    IRCCS San Raffaele Sci Inst, Via Olgettina 58, I-20132 Milan, Italy;

    IRCCS San Raffaele Sci Inst, Via Olgettina 58, I-20132 Milan, Italy;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    deamidation; enzymes; molecular docking; N-methylglycine; peptides;

    机译:脱酰胺酶分子对接N-甲基甘氨酸肽;

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