Chemical synthesis and serology of disaccharides and trisaccharides of phenolic glycolipid antigens from the leprosy bacillus and preparation of a disaccharide protein conjugate for serodiagnosis of leprosy

T. Fujiwara, S. W. Hunter, S. N. Cho, G. O. Aspinall, P. J. Brennan

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

We examined the structural requirements within the species-specific 3,6-di-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyrno syl-(1→2)-3-O-methyl-α-L-rhamnopyranose unit of the phenolic glycolipid I antigen of Mycobacterium leprae for binding to anti-glycolipid immunoglobulin M from human leprosy sera. We used chemically defined, partially deglycosylated fragments of phenolic glycolipid I, two other minor M. leprae-specific phenolic glycolipids (those containing 6-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyranosyl- (1→2)-3-O-methyl-α-L-rhamnopyranose and 3,6-di-O-methyl-β-D-glucopyranosyl-(1→[4)-3-O-methyl-α-L-rhamnopyranosyl -(1→2)-3-O-methyl-α-L-rhamnopyranose units), and phenolic glycolipids from other mycobacteria. Additionally, the trisaccharide of phenolic glycolipid I, the 3,6-di-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyran ose, the 6-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyranose, and the β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyranose disaccharides were synthesized and characterized, and their activities were examined. Only the phenolic glycolipids containing 3,6-di-O-methyl-β-D-glucopyranosyl at the nonreducing terminus were efficient in binding the anti-glycolipid immunoglobulin M, and the 3,6-di-O-methyl-β-D-glucopyranosyl-containing di- and trisaccharides were the most effective in inhibiting this binding. Thus, the 3,6-di-O-methyl-β-D-glucopyranosyl substituent was recognized as the primary antigen determinant in phenolic glycolipid I. With this information, bovine serum albumin containing reductively aminated 3,6-di-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-L-rhamnose was prepared and shown to be highly active in the serodiagnosis of leprosy.

Original languageEnglish
Pages (from-to)245-252
Number of pages8
JournalInfection and Immunity
Volume43
Issue number1
Publication statusPublished - 1984 Mar 8

Fingerprint

Trisaccharides
Disaccharides
Glycolipids
Serologic Tests
Leprosy
Serology
Bacillus
Antigens
Proteins
Immunoglobulin M
Mycobacterium leprae
Mycobacterium
Bovine Serum Albumin

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

@article{9f7cb24ba581499089c1d57f7a19f74c,
title = "Chemical synthesis and serology of disaccharides and trisaccharides of phenolic glycolipid antigens from the leprosy bacillus and preparation of a disaccharide protein conjugate for serodiagnosis of leprosy",
abstract = "We examined the structural requirements within the species-specific 3,6-di-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyrno syl-(1→2)-3-O-methyl-α-L-rhamnopyranose unit of the phenolic glycolipid I antigen of Mycobacterium leprae for binding to anti-glycolipid immunoglobulin M from human leprosy sera. We used chemically defined, partially deglycosylated fragments of phenolic glycolipid I, two other minor M. leprae-specific phenolic glycolipids (those containing 6-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyranosyl- (1→2)-3-O-methyl-α-L-rhamnopyranose and 3,6-di-O-methyl-β-D-glucopyranosyl-(1→[4)-3-O-methyl-α-L-rhamnopyranosyl -(1→2)-3-O-methyl-α-L-rhamnopyranose units), and phenolic glycolipids from other mycobacteria. Additionally, the trisaccharide of phenolic glycolipid I, the 3,6-di-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyran ose, the 6-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyranose, and the β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyranose disaccharides were synthesized and characterized, and their activities were examined. Only the phenolic glycolipids containing 3,6-di-O-methyl-β-D-glucopyranosyl at the nonreducing terminus were efficient in binding the anti-glycolipid immunoglobulin M, and the 3,6-di-O-methyl-β-D-glucopyranosyl-containing di- and trisaccharides were the most effective in inhibiting this binding. Thus, the 3,6-di-O-methyl-β-D-glucopyranosyl substituent was recognized as the primary antigen determinant in phenolic glycolipid I. With this information, bovine serum albumin containing reductively aminated 3,6-di-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-L-rhamnose was prepared and shown to be highly active in the serodiagnosis of leprosy.",
author = "T. Fujiwara and Hunter, {S. W.} and Cho, {S. N.} and Aspinall, {G. O.} and Brennan, {P. J.}",
year = "1984",
month = "3",
day = "8",
language = "English",
volume = "43",
pages = "245--252",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "1",

}

Chemical synthesis and serology of disaccharides and trisaccharides of phenolic glycolipid antigens from the leprosy bacillus and preparation of a disaccharide protein conjugate for serodiagnosis of leprosy. / Fujiwara, T.; Hunter, S. W.; Cho, S. N.; Aspinall, G. O.; Brennan, P. J.

In: Infection and Immunity, Vol. 43, No. 1, 08.03.1984, p. 245-252.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Chemical synthesis and serology of disaccharides and trisaccharides of phenolic glycolipid antigens from the leprosy bacillus and preparation of a disaccharide protein conjugate for serodiagnosis of leprosy

AU - Fujiwara, T.

AU - Hunter, S. W.

AU - Cho, S. N.

AU - Aspinall, G. O.

AU - Brennan, P. J.

PY - 1984/3/8

Y1 - 1984/3/8

N2 - We examined the structural requirements within the species-specific 3,6-di-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyrno syl-(1→2)-3-O-methyl-α-L-rhamnopyranose unit of the phenolic glycolipid I antigen of Mycobacterium leprae for binding to anti-glycolipid immunoglobulin M from human leprosy sera. We used chemically defined, partially deglycosylated fragments of phenolic glycolipid I, two other minor M. leprae-specific phenolic glycolipids (those containing 6-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyranosyl- (1→2)-3-O-methyl-α-L-rhamnopyranose and 3,6-di-O-methyl-β-D-glucopyranosyl-(1→[4)-3-O-methyl-α-L-rhamnopyranosyl -(1→2)-3-O-methyl-α-L-rhamnopyranose units), and phenolic glycolipids from other mycobacteria. Additionally, the trisaccharide of phenolic glycolipid I, the 3,6-di-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyran ose, the 6-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyranose, and the β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyranose disaccharides were synthesized and characterized, and their activities were examined. Only the phenolic glycolipids containing 3,6-di-O-methyl-β-D-glucopyranosyl at the nonreducing terminus were efficient in binding the anti-glycolipid immunoglobulin M, and the 3,6-di-O-methyl-β-D-glucopyranosyl-containing di- and trisaccharides were the most effective in inhibiting this binding. Thus, the 3,6-di-O-methyl-β-D-glucopyranosyl substituent was recognized as the primary antigen determinant in phenolic glycolipid I. With this information, bovine serum albumin containing reductively aminated 3,6-di-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-L-rhamnose was prepared and shown to be highly active in the serodiagnosis of leprosy.

AB - We examined the structural requirements within the species-specific 3,6-di-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyrno syl-(1→2)-3-O-methyl-α-L-rhamnopyranose unit of the phenolic glycolipid I antigen of Mycobacterium leprae for binding to anti-glycolipid immunoglobulin M from human leprosy sera. We used chemically defined, partially deglycosylated fragments of phenolic glycolipid I, two other minor M. leprae-specific phenolic glycolipids (those containing 6-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyranosyl- (1→2)-3-O-methyl-α-L-rhamnopyranose and 3,6-di-O-methyl-β-D-glucopyranosyl-(1→[4)-3-O-methyl-α-L-rhamnopyranosyl -(1→2)-3-O-methyl-α-L-rhamnopyranose units), and phenolic glycolipids from other mycobacteria. Additionally, the trisaccharide of phenolic glycolipid I, the 3,6-di-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyran ose, the 6-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyranose, and the β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyranose disaccharides were synthesized and characterized, and their activities were examined. Only the phenolic glycolipids containing 3,6-di-O-methyl-β-D-glucopyranosyl at the nonreducing terminus were efficient in binding the anti-glycolipid immunoglobulin M, and the 3,6-di-O-methyl-β-D-glucopyranosyl-containing di- and trisaccharides were the most effective in inhibiting this binding. Thus, the 3,6-di-O-methyl-β-D-glucopyranosyl substituent was recognized as the primary antigen determinant in phenolic glycolipid I. With this information, bovine serum albumin containing reductively aminated 3,6-di-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-L-rhamnose was prepared and shown to be highly active in the serodiagnosis of leprosy.

UR - http://www.scopus.com/inward/record.url?scp=0021353452&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021353452&partnerID=8YFLogxK

M3 - Article

VL - 43

SP - 245

EP - 252

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 1

ER -