• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

半乳糖鞘氨醇酰胺：新型 α-GalCer 类似物可探测 CD1d 的 F'-口袋。

Galactosylsphingamides: new α-GalCer analogues to probe the F'-pocket of CD1d.

机构信息

Laboratory for Medicinal Chemistry (FFW), Faculty of Pharmaceutical Sciences, UGent, Ottergemsesteenweg 460, B-9000, Ghent, Belgium.

Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA, 92037, USA.

出版信息

Sci Rep. 2017 Jun 27;7(1):4276. doi: 10.1038/s41598-017-04461-7.

DOI:10.1038/s41598-017-04461-7
PMID:28655912
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5487351/
Abstract

Invariant Natural Killer T-cells (iNKT-cells) are an attractive target for immune response modulation, as upon CD1d-mediated stimulation with KRN7000, a synthetic α-galactosylceramide, they produce a vast amount of cytokines. Here we present a synthesis that allows swift modification of the phytosphingosine side chain by amidation of an advanced methyl ester precursor. The resulting KRN7000 derivatives, termed α-galactosylsphingamides, were evaluated for their capacity to stimulate iNKT-cells. While introduction of the amide-motif in the phytosphingosine chain is tolerated for CD1d binding and TCR recognition, the studied α-galactosylsphingamides showed compromised antigenic properties.

摘要

不变自然杀伤 T 细胞（iNKT 细胞）是免疫反应调节的一个有吸引力的靶点，因为在 CD1d 介导的与 KRN7000（一种合成的α-半乳糖神经酰胺）的刺激下，它们会产生大量细胞因子。在这里，我们提出了一种通过酰胺化高级甲酯前体来快速修饰植物鞘氨醇侧链的合成方法。所得的 KRN7000 衍生物，称为α-半乳糖神经酰胺，因其刺激 iNKT 细胞的能力而得到评估。虽然酰胺基在植物鞘氨醇链中的引入可耐受 CD1d 结合和 TCR 识别，但所研究的α-半乳糖神经酰胺表现出抗原性降低的特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/346e/5487351/2e3e879bb6ec/41598_2017_4461_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/346e/5487351/b8e3497f8ed0/41598_2017_4461_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/346e/5487351/c6585ad17977/41598_2017_4461_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/346e/5487351/28b8b4ecc31c/41598_2017_4461_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/346e/5487351/5926cc907b58/41598_2017_4461_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/346e/5487351/b3eb43ce063b/41598_2017_4461_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/346e/5487351/d13ab12dab18/41598_2017_4461_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/346e/5487351/0c8d4dd5faa1/41598_2017_4461_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/346e/5487351/9f6f535bc714/41598_2017_4461_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/346e/5487351/b3d13ab2b128/41598_2017_4461_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/346e/5487351/2e3e879bb6ec/41598_2017_4461_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/346e/5487351/b8e3497f8ed0/41598_2017_4461_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/346e/5487351/c6585ad17977/41598_2017_4461_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/346e/5487351/28b8b4ecc31c/41598_2017_4461_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/346e/5487351/5926cc907b58/41598_2017_4461_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/346e/5487351/b3eb43ce063b/41598_2017_4461_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/346e/5487351/d13ab12dab18/41598_2017_4461_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/346e/5487351/0c8d4dd5faa1/41598_2017_4461_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/346e/5487351/9f6f535bc714/41598_2017_4461_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/346e/5487351/b3d13ab2b128/41598_2017_4461_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/346e/5487351/2e3e879bb6ec/41598_2017_4461_Fig10_HTML.jpg

相似文献

1
Galactosylsphingamides: new α-GalCer analogues to probe the F'-pocket of CD1d.半乳糖鞘氨醇酰胺：新型 α-GalCer 类似物可探测 CD1d 的 F'-口袋。
Sci Rep. 2017 Jun 27;7(1):4276. doi: 10.1038/s41598-017-04461-7.
2
3,4-Dideoxy-3,3,4,4-tetrafluoro- and 4-OH epimeric 3-deoxy-3,3-difluoro-α-GalCer analogues: Synthesis and biological evaluation on human iNKT cells stimulation.3,4-二脱氧-3,3,4,4-四氟代和 4-OH 差向异构体 3-脱氧-3,3-二氟-α-GalCer 类似物的合成及对人 iNKT 细胞刺激的生物学评价。
Eur J Med Chem. 2019 Sep 15;178:195-213. doi: 10.1016/j.ejmech.2019.05.069. Epub 2019 May 29.
3
Photo effect on the CD1d-binding ability of azobenzene-attached analogues of α-GalCer.苯偶氮键合的α-GalCer 类似物的光致异构化对 CD1d 结合能力的影响。
Bioorg Med Chem Lett. 2020 Mar 1;30(5):126960. doi: 10.1016/j.bmcl.2020.126960. Epub 2020 Jan 11.
4
The molecular basis for recognition of CD1d/α-galactosylceramide by a human non-Vα24 T cell receptor.人类非 Vα24 T 细胞受体识别 CD1d/α-半乳糖神经酰胺的分子基础。
PLoS Biol. 2012;10(10):e1001412. doi: 10.1371/journal.pbio.1001412. Epub 2012 Oct 23.
5
Structure-activity relationship studies of Bz amide-containing α-GalCer derivatives as natural killer T cell modulators.含 Bz 酰胺的α-GalCer 衍生物作为自然杀伤 T 细胞调节剂的构效关系研究。
Bioorg Med Chem Lett. 2019 Apr 15;29(8):970-973. doi: 10.1016/j.bmcl.2019.02.018. Epub 2019 Feb 18.
6
The Vα14 invariant natural killer T cell TCR forces microbial glycolipids and CD1d into a conserved binding mode.Vα14 不变自然杀伤 T 细胞 TCR 将微生物糖脂和 CD1d 强制形成一种保守的结合模式。
J Exp Med. 2010 Oct 25;207(11):2383-93. doi: 10.1084/jem.20101335. Epub 2010 Oct 4.
7
3-fluoro- and 3,3-difluoro-3,4-dideoxy-KRN7000 analogues as new potent immunostimulator agents: total synthesis and biological evaluation in human invariant natural killer T cells and mice.3-氟-和 3,3-二氟-3,4-二去氧-KRN7000 类似物作为新型有效的免疫刺激剂：在人不变自然杀伤 T 细胞和小鼠中的全合成和生物学评价。
J Med Chem. 2012 Feb 9;55(3):1227-41. doi: 10.1021/jm201368m. Epub 2012 Feb 1.
8
The GM2 ganglioside inhibits iNKT cell responses in a CD1d-dependent manner.神经节苷脂 GM2 以 CD1d 依赖的方式抑制 iNKT 细胞反应。
Mol Genet Metab. 2018 Sep;125(1-2):161-167. doi: 10.1016/j.ymgme.2018.07.005. Epub 2018 Jul 18.
9
Structure-Function Implications of the Ability of Monoclonal Antibodies Against α-Galactosylceramide-CD1d Complex to Recognize β-Mannosylceramide Presentation by CD1d.α-半乳糖神经酰胺-CD1d 复合物单抗识别 CD1d 呈递 β-甘露糖神经酰胺的结构-功能意义。
Front Immunol. 2019 Oct 9;10:2355. doi: 10.3389/fimmu.2019.02355. eCollection 2019.
10
Amide analogues of CD1d agonists modulate iNKT-cell-mediated cytokine production.酰胺类似物的 CD1d 激动剂调节 iNKT 细胞介导的细胞因子产生。
ACS Chem Biol. 2012 May 18;7(5):847-55. doi: 10.1021/cb2005017. Epub 2012 Feb 29.

引用本文的文献

1
State of play in the molecular presentation and recognition of anti-tumor lipid-based analogues.抗肿瘤脂质类似物的分子呈现与识别研究进展
Front Immunol. 2024 Nov 28;15:1479382. doi: 10.3389/fimmu.2024.1479382. eCollection 2024.
2
An immunostimulatory glycolipid that blocks SARS-CoV-2, RSV, and influenza infections in vivo.一种免疫刺激糖脂，可在体内阻断 SARS-CoV-2、RSV 和流感感染。
Nat Commun. 2023 Jul 5;14(1):3959. doi: 10.1038/s41467-023-39738-1.
3
The NKT cell TCR repertoire can accommodate structural modifications to the lipid and orientation of the terminal carbohydrate of iGb3.

本文引用的文献

1
Non-glycosidic compounds can stimulate both human and mouse iNKT cells.非糖苷化合物可刺激人和小鼠的iNKT细胞。
Eur J Immunol. 2016 May;46(5):1224-34. doi: 10.1002/eji.201546114. Epub 2016 Mar 1.
2
Heteroaromatic Moieties in the Sphingosine Backbone of α-Galactosylceramides for Noncovalent Interactions with CD1d.用于与CD1d进行非共价相互作用的α-半乳糖神经酰胺鞘氨醇骨架中的杂芳族部分。
ACS Med Chem Lett. 2012 Jan 10;3(2):151-4. doi: 10.1021/ml200278u. eCollection 2012 Feb 9.
3
Synthesis and biological evaluation of α-galactosylceramide analogues with heteroaromatic rings and varying positions of a phenyl group in the sphingosine backbone.
自然杀伤T细胞（NKT细胞）的T细胞受体（TCR）库能够适应iGb3（异麦芽三糖）脂质和末端碳水化合物方向的结构修饰。
RSC Adv. 2022 Jun 22;12(29):18493-18500. doi: 10.1039/d2ra02373c.
4
A molecular switch in mouse CD1d modulates natural killer T cell activation by α-galactosylsphingamides.鼠 CD1d 中的分子开关调节 α-半乳糖神经酰胺激活自然杀伤 T 细胞。
J Biol Chem. 2019 Sep 27;294(39):14345-14356. doi: 10.1074/jbc.RA119.009963. Epub 2019 Aug 7.
5
Structural basis of NKT cell inhibition using the T-cell receptor-blocking anti-CD1d antibody 1B1.使用 T 细胞受体阻断型抗 CD1d 抗体 1B1 抑制 NKT 细胞的结构基础。
J Biol Chem. 2019 Aug 30;294(35):12947-12956. doi: 10.1074/jbc.RA119.009403. Epub 2019 Jul 11.
6
Immunometabolic Activation of Invariant Natural Killer T Cells.固有自然杀伤 T 细胞的免疫代谢激活
Front Immunol. 2018 May 28;9:1192. doi: 10.3389/fimmu.2018.01192. eCollection 2018.
具有杂环和不同位置苯基团的神经酰胺类似物的合成及生物评价。
J Med Chem. 2013 Sep 12;56(17):7100-9. doi: 10.1021/jm400949h. Epub 2013 Aug 26.
4
Synthesis and biological evaluation of truncated α-galactosylceramide derivatives focusing on cytokine induction profile.聚焦细胞因子诱导谱的α-半乳糖神经酰胺衍生物的合成与生物学评价。
Bioorg Med Chem. 2012 May 1;20(9):2850-9. doi: 10.1016/j.bmc.2012.03.025. Epub 2012 Mar 20.
5
Galactose-modified iNKT cell agonists stabilized by an induced fit of CD1d prevent tumour metastasis.半乳糖基化 iNKT 细胞激动剂通过 CD1d 的诱导契合稳定，可预防肿瘤转移。
EMBO J. 2011 Jun 1;30(11):2294-305. doi: 10.1038/emboj.2011.145. Epub 2011 May 6.
6
Mechanism of regulation of autoimmunity by iNKT cells.NKT 细胞调控自身免疫的机制。
Cytokine. 2011 Mar;53(3):263-70. doi: 10.1016/j.cyto.2010.11.001. Epub 2010 Dec 23.
7
The Vα14 invariant natural killer T cell TCR forces microbial glycolipids and CD1d into a conserved binding mode.Vα14 不变自然杀伤 T 细胞 TCR 将微生物糖脂和 CD1d 强制形成一种保守的结合模式。
J Exp Med. 2010 Oct 25;207(11):2383-93. doi: 10.1084/jem.20101335. Epub 2010 Oct 4.
8
Synthesis of immunostimulatory alpha-C-galactosylceramide glycolipids via Sonogashira coupling, asymmetric epoxidation, and trichloroacetimidate-mediated epoxide opening.通过 Sonogashira 偶联、不对称环氧化和三氯乙酰亚胺酯介导的环氧化物开环反应合成免疫刺激性的α-C-半乳糖神经酰胺糖脂。
Org Lett. 2010 Jul 2;12(13):2974-7. doi: 10.1021/ol1009976.
9
Lipid binding orientation within CD1d affects recognition of Borrelia burgorferi antigens by NKT cells.脂质结合构象在 CD1d 分子内影响 NKT 细胞对伯氏疏螺旋体抗原的识别。
Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1535-40. doi: 10.1073/pnas.0909479107. Epub 2009 Dec 30.
10
Syntheses and biological activities of KRN7000 analogues having aromatic residues in the acyl and backbone chains with varying stereochemistry.具有不同立体化学的酰基和主链中芳基残基的 KRN7000 类似物的合成及生物活性。
Bioorg Med Chem Lett. 2010 Feb 1;20(3):814-8. doi: 10.1016/j.bmcl.2009.12.103. Epub 2010 Jan 4.