Program in Innate Immunity and Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Chan Medical School, Worcester MA 01605, USA.
Chemistry and Biochemistry, University of Delaware, Newark, Delaware, USA.
Innate Immun. 2023 Nov;29(8):186-200. doi: 10.1177/17534259231207198. Epub 2023 Oct 13.
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.
NOD1 和 NOD2 感知小的细菌肽聚糖片段，通常称为肽聚糖，这些肽聚糖片段进入细胞质。这些肽聚糖包括 iE-DAP 和 MDP，分别是 NOD1 和 NOD2 的最小激动剂。在这里，我们合成并验证了炔基修饰的肽聚糖，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外源暴露于肽聚糖有反应，但尚不清楚这些先天免疫激活剂如何进入其细胞质内的先天免疫受体 NOD1 和 NOD2。肽聚糖进入这些细胞质内先天免疫受体的细胞内运输和运输机制是我们理解这些关键宿主反应的主要空白。这里开发的点击化学激活剂将特别有助于破译 NOD1 和 NOD2 先天免疫感应的潜在细胞生物学和生物化学。
