Synthesis, Structural Elucidation, And Biochemical Analysis of Immunoactive Glucuronosyl Diacylglycerides of Mycobacteria and Corynebacteria

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• 作者：Benjamin Cao ; Xingqiang Chen ; Yoshiki Yamaryo-Botte ; Mark B. Richardson ; Kirstee L. Martin ; George N. Khairallah ; Thusita W.T. Rupasinghe ; Roisin M. O鈥橣laherty ; Richard A.J. O鈥橦air ; Julie E. Ralton ; Paul K. Crellin ; Ross L. Coppel ; Malcolm J. McConville ; Spencer J. Williams
• 刊名：The Journal of Organic Chemistry
• 出版年：2013
• 出版时间：March 15, 2013
• 年：2013
• 卷：78
• 期：6
• 页码：2175-2190
• 全文大小：596K
• 年卷期：v.78,no.6(March 15, 2013)
• ISSN：1520-6904

文摘

Glucuronosyl diacylglycerides (GlcAGroAc₂) are functionally important glycolipids and membrane anchors for cell wall lipoglycans in the Corynebacteria. Here we describe the complete synthesis of distinct acyl-isoforms of GlcAGroAc₂ bearing both acylation patterns of (R)-tuberculostearic acid (C_19:0) and palmitic acid (C_16:0) and their mass spectral characterization. Collision-induced fragmentation mass spectrometry identified characteristic fragment ions that were used to develop 鈥渞ules鈥?allowing the assignment of the acylation pattern as C_19:0 (sn-1), C_16:0 (sn-2) in the natural product from Mycobacterium smegmatis, and the structural assignment of related C_18:1 (sn-1), C_16:0 (sn-2) GlcAGroAc₂ glycolipids from M. smegmatis and Corynebacterium glutamicum. A synthetic hydrophobic octyl glucuronoside was used to characterize the GDP-mannose-dependent mannosyltransferase MgtA from C. glutamicum that extends GlcAGroAc₂. This enzyme is an Mg²⁺/Mn²⁺-dependent metalloenzyme that undergoes dramatic activation upon reduction with dithiothreitol.