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 language | English |
|---|---|
| Pages (from-to) | 187-208 |
| Number of pages | 22 |
| Journal | Glycoconjugate Journal |
| Volume | 2 |
| Issue number | 3-4 |
| DOIs | |
| Publication status | Published - 1985 Sep 1 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology
- Cell Biology
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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 journal › Article
TY - JOUR
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.
PY - 1985/9/1
Y1 - 1985/9/1
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.
UR - http://www.scopus.com/inward/record.url?scp=0022417032&partnerID=8YFLogxK
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U2 - 10.1007/BF01049268
DO - 10.1007/BF01049268
M3 - Article
AN - SCOPUS:0022417032
VL - 2
SP - 187
EP - 208
JO - Glycoconjugate Journal
JF - Glycoconjugate Journal
SN - 0282-0080
IS - 3-4
ER -