Lactone-driven ester-to-amide derivatization for sialic acid linkage-specific alkylamidation (LEAD-SALSA).
Lactone-driven ester-to-amide derivatization for sialic acid linkage-specific alkylamidation (LEAD-SALSA).
复制标题
内酯驱动的酯到酰胺衍生化，用于唾液酸键特异性烷基酰胺化 (LEAD-SALSA)。
作者：
J. Furukawa;H. Hanamatsu;Takashi Nishikaze;H. Manya;Nobuaki Miura;H. Yagi;Ikuko Yokota;K. Akasaka;T. Endo;M. Kanagawa;N. Iwasaki;Koichi Tanaka
唾液酸通过不同的键连接到聚糖链的非还原末端，与特定的相互作用和生理事件相关。唾液酸的键特异性衍生化对于通过质谱法（MS）区分唾液酸，特别是对于由唾液酸键类型控制的事件具有极大的意义。在本研究中，我们证明了酯化唾液酸寡糖的β-2，3/8-唾液酸键特异性酰胺化可以通过分子内内酯实现。用于唾液酸键特异性烷基酰胺化的内酯驱动的酯-酰胺衍生化方法（称为LEAD-SALSA）采用溶液中酯-酰胺转化，通过与优选胺混合，从其酯形式直接生成稳定和唾液酸键特异性聚糖酰胺，通过比较酯化和酰胺化聚糖的信号，轻松分配唾液酸键。使用这种方法，我们证明了在小鼠衰老过程中心肌组织中N-聚糖的积累。此外，我们发现，内酯的稳定性是重要的酯到酰胺的转化的基础上的实验和DFT计算的反应能量的内酯形成。通过利用内酯形成的能量差，LEAD-SALSA方法不仅可用于唾液酸键特异性衍生化，而且可用于区分连接到唾液酸的半乳糖的分支结构。这种简化和直接的唾液酸聚糖识别将促进唾液酸化糖缀合物的重要研究。
Sialic acid attached to non-reducing ends of glycan chains via different linkages is associated with specific interactions and physiological events. Linkage-specific derivatization of sialic acid is of great interest for distinguishing sialic acids by mass spectrometry (MS), specifically for events governed by the sialyl linkage types. In the present study, we demonstrate that -2,3/8-sialyl linkage-specific amidation of esterified sialyloligosaccharides can be achieved via an intramolecular lactone. The method of Lactone-driven ester-to-amide derivatization for sialic acid linkage-specific alkylamidation, termed LEAD-SALSA, employs in-solution ester-to-amide conversion to directly generate stable and sialyl linkage-specific glycan amides from their ester form by mixing with a preferred amine, resulting the easy assignments of sialyl linkages by comparing the signals of esterified and amidated glycan. Using this approach, we demonstrate an accumulation of altered N-glycans in cardiac muscle tissue during mouse aging. Furthermore, we find that the stability of lactone is important for ester-to-amide conversion based on experiments and DFT calculations of reaction energies for lactone formation. By using energy differences of lactone formation, the LEAD-SALSA method can be used not only for the sialyl linkage-specific derivatization, but also for the distinguishing the branching structure of galactose linked to sialic acid. This simplified and direct sialylglycan discrimination will facilitate important studies on sialylated glycoconjugates.
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高压基质辅助激光解吸/电离傅里叶变换质谱离子源，用于不稳定生物分子的热稳定。
DOI：
10.1002/rcm.447
发表时间：
2001
期刊：
Rapid communications in mass spectrometry : RCM.
影响因子：
--
作者：
O'Connor,PB;Costello,CE
通讯作者：
Costello,CE
影响因子：
7.4
作者：
Holst, Stephanie;Heijs, Bram;Wuhrer, Manfred
通讯作者：
Wuhrer, Manfred
影响因子：
2
作者：
Kang, P;Mechref, Y;Novotny, MV
通讯作者：
Novotny, MV
影响因子：
4.4
作者：
Alley, William R., Jr.;Novotny, Milos V.
通讯作者：
Novotny, Milos V.