Synthesis of Neoglycoproteins containing the 3,6-di-O-methyl-β-d-glucopyranosyl epitope and their use in serodiagnosis of leprosy

Delphi Chatterjee, James T. Douglas, Sang Nae Cho, Thomas H. Rea, Robert H. Gelber, Gerald O. Aspinall, Patrick J. Brennan

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

A stratagem for the synthesis of neoglycoproteins suitable for the selective serodiagnosis of leprosy is described in which synthetic 3,6-di-O-methyl-β-d-glucopyranose, the epitope of phenolic glycolipid I from Mycobacterium leprae, was used. Condensation of 8-methoxycarbonyloctanol with the acetobromo derivative of 3,6-di-O-methylglucose gave 8-methoxycarbonyloctyl 2,4-di-O-acetyl-3,6-di-O-methyl-β-d-glucopyranoside in 65% yield, and with absolute stereospecificity for the β anomer. The deacylated product was converted to the crystalline hydrazide and coupled to bovine gamma globulin, bovine serum albumin and poly-d-lysine via intermediate acyl azide formation to produce the 8-carbonyloctyl 3,6-di-O-methyl-β-d-glucopyranosyl polypeptides. The neoglycoproteins were highly sensitive in ELISA and emulated the specificity of the native glycolipid in analysis of sera from patients throughout the spectrum of leprosy and from different geographical regions. The 8-carbonyloctyl 3,6-di-O-methyl-α-d-glucopyranoside-bovine serum albumin was also synthesized and shown to have about one-half the activity of the β-linked neoglycoprotein. A different synthetic approach produced the 8-carbonyloctyl 4-O-(3′,6′-di-O-methyl-β-d-glucopyranosyl)-α-l-rhamnopyranoside-bovine serum albumin which was also highly sensitive and specific for the serodiagnosis of leprosy. The presence of the second sugar unit, similar to that in the native glycolipid but for the absence of O-methyl groups, seemed to provide a probe with greater felicity for the serological detection of tuberculoid leprosy. Thus, the results indicate that highly sensitive and specific antigen probes for the serodiagnosis of leprosy can be constructed based only on the terminal one or two sugars of phenolic glycolipid I, and the synthetic approach leads to the formation of haptens with absolute stereospecificity.

Original languageEnglish
Pages (from-to)187-208
Number of pages22
JournalGlycoconjugate Journal
Volume2
Issue number3-4
DOIs
Publication statusPublished - 1985 Sep 1

Fingerprint

Glycolipids
Serologic Tests
Leprosy
Bovine Serum Albumin
Epitopes
Glycoproteins
Sugars
Geographical regions
Azides
Haptens
gamma-Globulins
Tuberculoid Leprosy
Lysine
Condensation
Crystalline materials
Derivatives
Antigens
Peptides
Enzyme-Linked Immunosorbent Assay
Serum

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Chatterjee, Delphi ; Douglas, James T. ; Cho, Sang Nae ; Rea, Thomas H. ; Gelber, Robert H. ; Aspinall, Gerald O. ; Brennan, Patrick J. / Synthesis of Neoglycoproteins containing the 3,6-di-O-methyl-β-d-glucopyranosyl epitope and their use in serodiagnosis of leprosy. In: Glycoconjugate Journal. 1985 ; Vol. 2, No. 3-4. pp. 187-208.
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abstract = "A stratagem for the synthesis of neoglycoproteins suitable for the selective serodiagnosis of leprosy is described in which synthetic 3,6-di-O-methyl-β-d-glucopyranose, the epitope of phenolic glycolipid I from Mycobacterium leprae, was used. Condensation of 8-methoxycarbonyloctanol with the acetobromo derivative of 3,6-di-O-methylglucose gave 8-methoxycarbonyloctyl 2,4-di-O-acetyl-3,6-di-O-methyl-β-d-glucopyranoside in 65{\%} yield, and with absolute stereospecificity for the β anomer. The deacylated product was converted to the crystalline hydrazide and coupled to bovine gamma globulin, bovine serum albumin and poly-d-lysine via intermediate acyl azide formation to produce the 8-carbonyloctyl 3,6-di-O-methyl-β-d-glucopyranosyl polypeptides. The neoglycoproteins were highly sensitive in ELISA and emulated the specificity of the native glycolipid in analysis of sera from patients throughout the spectrum of leprosy and from different geographical regions. The 8-carbonyloctyl 3,6-di-O-methyl-α-d-glucopyranoside-bovine serum albumin was also synthesized and shown to have about one-half the activity of the β-linked neoglycoprotein. A different synthetic approach produced the 8-carbonyloctyl 4-O-(3′,6′-di-O-methyl-β-d-glucopyranosyl)-α-l-rhamnopyranoside-bovine serum albumin which was also highly sensitive and specific for the serodiagnosis of leprosy. The presence of the second sugar unit, similar to that in the native glycolipid but for the absence of O-methyl groups, seemed to provide a probe with greater felicity for the serological detection of tuberculoid leprosy. Thus, the results indicate that highly sensitive and specific antigen probes for the serodiagnosis of leprosy can be constructed based only on the terminal one or two sugars of phenolic glycolipid I, and the synthetic approach leads to the formation of haptens with absolute stereospecificity.",
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Synthesis of Neoglycoproteins containing the 3,6-di-O-methyl-β-d-glucopyranosyl epitope and their use in serodiagnosis of leprosy. / Chatterjee, Delphi; Douglas, James T.; Cho, Sang Nae; Rea, Thomas H.; Gelber, Robert H.; Aspinall, Gerald O.; Brennan, Patrick J.

In: Glycoconjugate Journal, Vol. 2, No. 3-4, 01.09.1985, p. 187-208.

Research output: Contribution to journalArticle

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T1 - Synthesis of Neoglycoproteins containing the 3,6-di-O-methyl-β-d-glucopyranosyl epitope and their use in serodiagnosis of leprosy

AU - Chatterjee, Delphi

AU - Douglas, James T.

AU - Cho, Sang Nae

AU - Rea, Thomas H.

AU - Gelber, Robert H.

AU - Aspinall, Gerald O.

AU - Brennan, Patrick J.

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N2 - A stratagem for the synthesis of neoglycoproteins suitable for the selective serodiagnosis of leprosy is described in which synthetic 3,6-di-O-methyl-β-d-glucopyranose, the epitope of phenolic glycolipid I from Mycobacterium leprae, was used. Condensation of 8-methoxycarbonyloctanol with the acetobromo derivative of 3,6-di-O-methylglucose gave 8-methoxycarbonyloctyl 2,4-di-O-acetyl-3,6-di-O-methyl-β-d-glucopyranoside in 65% yield, and with absolute stereospecificity for the β anomer. The deacylated product was converted to the crystalline hydrazide and coupled to bovine gamma globulin, bovine serum albumin and poly-d-lysine via intermediate acyl azide formation to produce the 8-carbonyloctyl 3,6-di-O-methyl-β-d-glucopyranosyl polypeptides. The neoglycoproteins were highly sensitive in ELISA and emulated the specificity of the native glycolipid in analysis of sera from patients throughout the spectrum of leprosy and from different geographical regions. The 8-carbonyloctyl 3,6-di-O-methyl-α-d-glucopyranoside-bovine serum albumin was also synthesized and shown to have about one-half the activity of the β-linked neoglycoprotein. A different synthetic approach produced the 8-carbonyloctyl 4-O-(3′,6′-di-O-methyl-β-d-glucopyranosyl)-α-l-rhamnopyranoside-bovine serum albumin which was also highly sensitive and specific for the serodiagnosis of leprosy. The presence of the second sugar unit, similar to that in the native glycolipid but for the absence of O-methyl groups, seemed to provide a probe with greater felicity for the serological detection of tuberculoid leprosy. Thus, the results indicate that highly sensitive and specific antigen probes for the serodiagnosis of leprosy can be constructed based only on the terminal one or two sugars of phenolic glycolipid I, and the synthetic approach leads to the formation of haptens with absolute stereospecificity.

AB - A stratagem for the synthesis of neoglycoproteins suitable for the selective serodiagnosis of leprosy is described in which synthetic 3,6-di-O-methyl-β-d-glucopyranose, the epitope of phenolic glycolipid I from Mycobacterium leprae, was used. Condensation of 8-methoxycarbonyloctanol with the acetobromo derivative of 3,6-di-O-methylglucose gave 8-methoxycarbonyloctyl 2,4-di-O-acetyl-3,6-di-O-methyl-β-d-glucopyranoside in 65% yield, and with absolute stereospecificity for the β anomer. The deacylated product was converted to the crystalline hydrazide and coupled to bovine gamma globulin, bovine serum albumin and poly-d-lysine via intermediate acyl azide formation to produce the 8-carbonyloctyl 3,6-di-O-methyl-β-d-glucopyranosyl polypeptides. The neoglycoproteins were highly sensitive in ELISA and emulated the specificity of the native glycolipid in analysis of sera from patients throughout the spectrum of leprosy and from different geographical regions. The 8-carbonyloctyl 3,6-di-O-methyl-α-d-glucopyranoside-bovine serum albumin was also synthesized and shown to have about one-half the activity of the β-linked neoglycoprotein. A different synthetic approach produced the 8-carbonyloctyl 4-O-(3′,6′-di-O-methyl-β-d-glucopyranosyl)-α-l-rhamnopyranoside-bovine serum albumin which was also highly sensitive and specific for the serodiagnosis of leprosy. The presence of the second sugar unit, similar to that in the native glycolipid but for the absence of O-methyl groups, seemed to provide a probe with greater felicity for the serological detection of tuberculoid leprosy. Thus, the results indicate that highly sensitive and specific antigen probes for the serodiagnosis of leprosy can be constructed based only on the terminal one or two sugars of phenolic glycolipid I, and the synthetic approach leads to the formation of haptens with absolute stereospecificity.

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