Synthesis and validation of click-modified NOD1/2 agonists.

Synthesis and validation of click-modified NOD1/2 agonists.
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点击修饰的NOD1/2激动剂的合成和验证。

DOI:
10.1177/17534259231207198
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发表时间:
2023-11
期刊:
影响因子:
3.2
通讯作者:
Grimes, Catherine L.
Grimes, Catherine L.
中科院分区:
生物学4区
文献类型:
--
作者:
Bharadwaj, Ravi;Anonick, Madison V.;Jaiswal, Swati;Mashayekh, Siavash;Brown, Ashley;Wodzanowski, Kimberly A.;Okuda, Kendi;Silverman, Neal;Grimes, Catherine L.

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NOD1和NOD2能感知进入细胞质的小细菌肽聚糖片段,通常被称为多肽。这些多肽包括iE-DAP和MDP,它们分别是NOD1和NOD2的最小激动剂。在这里,我们合成并验证了炔修饰的多肽,iE-DAP-Alk和MDP-Alk,用于点击化学反应。虽然人们早就知道,许多细胞类型对细胞外暴露于多肽有反应,但尚不清楚这些先天免疫激活剂如何进入其细胞质先天免疫受体NOD1和NOD2。多肽进入这些细胞质先天免疫受体的亚细胞运输和运输机制是我们对这些关键宿主反应理解的主要空白。这里开发的点击化学激活激动剂将特别强大,可以破译NOD1和NOD2先天免疫感知的潜在细胞生物学和生物化学。
NOD1 and NOD2 sense small bacterial peptidoglycan fragments, often called muropeptides, that access the cytosol. These muropeptides include iE-DAP and MDP, the minimal agonists for NOD1 and NOD2, respectively. Here, we synthesized and validated alkyne-modified muropeptides, iE-DAP-Alk and MDP-Alk, for use in click-chemistry reactions. While it has long been known that many cell types respond to extracellular exposure to muropeptides, it is unclear how these innate immune activators access their cytosolic innate immune receptors, NOD1 and NOD2. The subcellular trafficking and transport mechanisms by which muropeptides access these cytosolic innate immune receptors are a major gap in our understanding of these critical host responses. The click-chemistry-enabled agonists developed here will be particularly powerful to decipher the underlying cell biology and biochemistry of NOD1 and NOD2 innate immune sensing.
宿主代谢和免疫系统界面处的共生细菌。
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