A modified synthesis and serological evaluation of neoglycoproteins containing the natural disaccharide of PGL-I from Mycobacterium leprae.

Abstract

In order to generate substantial amounts of neoglycoconjugate needed for commercialization of diagnostic kits and high-throughput detection of leprosy, we developed a facile and high-yield synthesis of the corresponding disaccharide. Herein, the non-reducing disaccharide segment of phenolic glycolipid I from Mycobacterium leprae, O-(3,6-di-O-methyl-beta-D-glucopyranosyl)-(1-->4)-O-2,3-di-O-methyl-alpha-L-rhamnopyranose was synthesized by an improved procedure. The disaccharide was efficiently conjugated to bovine/human serum albumin, via acyl-azide intermediate, to form natural disaccharide-BSA/HSA neoglycoproteins that showed a high activity in serodiagnosis of leprosy. The disaccharide incorporated into the proteins was accurately measured by MALDI-TOF mass spectrometry. The serological activities of the neoglycoproteins against pooled human lepromatous leprosy sera were measured by ELISA and they were detectable at picogram amounts.

• Authors: Jian Zhang, Delphi Chatterjee, Patrick J Brennan, John S Spencer, Avraham Liav
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 20 Issue 11 Pg. 3250-3 (Jun 01 2010) ISSN: 1464-3405 [Electronic] England
• PMID: 20462755 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Antigens, Bacterial
• Disaccharides
• Glycolipids
• Glycoproteins
• phenolic glycolipid I, Mycobacterium leprae

Topics

• Antigens, Bacterial (chemistry)
• Carbohydrate Sequence
• Disaccharides (chemistry)
• Enzyme-Linked Immunosorbent Assay
• Glycolipids (chemistry)
• Glycoproteins (blood, chemical synthesis, chemistry)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization