Synthesis of a model trisaccharide for studying the interplay between the anti α-Gal antibody and the trans-sialidase reactions in Trypanosoma cruzi

Trypanosoma cruzi, the etiologic agent of Chagas disease, is covered by a dense glycocalix mainly composed by glycoproteins called mucins which are also the acceptors of sialic acid in a reaction catalyzed by a trans-sialidase (TcTS). Sialylation of trypomastigote mucins protects the parasite from l...

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Veröffentlicht in:Carbohydrate research 2017-10, Vol.450, p.30-37
Hauptverfasser: Giorgi, M. Eugenia, Lopez, Rosana, Agusti, Rosalia, Marino, Carla, de Lederkremer, Rosa M.
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description Trypanosoma cruzi, the etiologic agent of Chagas disease, is covered by a dense glycocalix mainly composed by glycoproteins called mucins which are also the acceptors of sialic acid in a reaction catalyzed by a trans-sialidase (TcTS). Sialylation of trypomastigote mucins protects the parasite from lysis by the anti α-Galp antibodies from serum. The TcTS is essential for the infection process since T. cruzi is unable to biosynthesize sialic acid. The enzyme specifically transfers it from a terminal β-d-Galp unit in the host glycoconjugate to terminal β-d-Galp units in the parasite mucins to construct the d-NeuNAc(α2→3)β-d-Galp motif. On the other hand, although galactose is the most abundant sugar in mucins of both, the infective trypomastigotes and the insect stage epimastigotes, α-d-Galp is only present in the infective stage whereas β-d-Galf is characteristic of the epimastigote stage of the less virulent strains. Neither α-d-Galp nor d-Galf is acceptor of sialic acid. In the mucins, some of the oligosaccharides are branched with terminal β-d-Galp units to be able to accept sialic acid in the TcTS reaction. Based on previous reports showing that anti α-Galp antibodies only partially colocalize with sialic acid, we have undertaken the synthesis of the trisaccharide α-d-Galp(1→3)-[β-d-Galp(1→6)]-d-Galp, the smallest structure containing both, the antigenic d-Galp(α1→3)-d-Galp unit and the sialic acid-acceptor β-d-Galp unit. The trisaccharide was obtained as the 6-aminohexyl glycoside to facilitate further conjugation for biochemical studies. The synthetic approach involved the α-galactosylation at O-4 of a suitable precursor of the reducing end, followed by β-galactosylation at O-6 of the same precursor and introduction of the 6-aminohexyl aglycone. The fully deprotected trisaccharide was successfully sialylated by TcTS using either 3′-sialyllactose or fetuin as donors. The product, 6-aminohexyl α-d-NeuNAc(2→3)-β-d-Galp(1→6)-[α-d-Galp(1→3)]-β-d-Galp, was purified and characterized. [Display omitted] •The α-Gal (1–3)Gal motif and a β-Galp terminal unit are characteristic of Trypanosoma cruzi mucins.•The model 6-aminohexyl α-d-Galp(1 → 3)-[β-d-Galp(1 → 6)]-d-Galp was synthesized•Sialylation by T. cruzi trans-sialidase occurs at O-3 of the β-d-Galp unit.•HPAEC was used to follow sialylation with sialyllactose as donor.•The trisaccharide and the tetrasaccharide are tools for immunological studies.
doi_str_mv 10.1016/j.carres.2017.08.007
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Eugenia ; Lopez, Rosana ; Agusti, Rosalia ; Marino, Carla ; de Lederkremer, Rosa M.</creator><creatorcontrib>Giorgi, M. Eugenia ; Lopez, Rosana ; Agusti, Rosalia ; Marino, Carla ; de Lederkremer, Rosa M.</creatorcontrib><description>Trypanosoma cruzi, the etiologic agent of Chagas disease, is covered by a dense glycocalix mainly composed by glycoproteins called mucins which are also the acceptors of sialic acid in a reaction catalyzed by a trans-sialidase (TcTS). Sialylation of trypomastigote mucins protects the parasite from lysis by the anti α-Galp antibodies from serum. The TcTS is essential for the infection process since T. cruzi is unable to biosynthesize sialic acid. The enzyme specifically transfers it from a terminal β-d-Galp unit in the host glycoconjugate to terminal β-d-Galp units in the parasite mucins to construct the d-NeuNAc(α2→3)β-d-Galp motif. On the other hand, although galactose is the most abundant sugar in mucins of both, the infective trypomastigotes and the insect stage epimastigotes, α-d-Galp is only present in the infective stage whereas β-d-Galf is characteristic of the epimastigote stage of the less virulent strains. Neither α-d-Galp nor d-Galf is acceptor of sialic acid. In the mucins, some of the oligosaccharides are branched with terminal β-d-Galp units to be able to accept sialic acid in the TcTS reaction. Based on previous reports showing that anti α-Galp antibodies only partially colocalize with sialic acid, we have undertaken the synthesis of the trisaccharide α-d-Galp(1→3)-[β-d-Galp(1→6)]-d-Galp, the smallest structure containing both, the antigenic d-Galp(α1→3)-d-Galp unit and the sialic acid-acceptor β-d-Galp unit. The trisaccharide was obtained as the 6-aminohexyl glycoside to facilitate further conjugation for biochemical studies. The synthetic approach involved the α-galactosylation at O-4 of a suitable precursor of the reducing end, followed by β-galactosylation at O-6 of the same precursor and introduction of the 6-aminohexyl aglycone. The fully deprotected trisaccharide was successfully sialylated by TcTS using either 3′-sialyllactose or fetuin as donors. The product, 6-aminohexyl α-d-NeuNAc(2→3)-β-d-Galp(1→6)-[α-d-Galp(1→3)]-β-d-Galp, was purified and characterized. [Display omitted] •The α-Gal (1–3)Gal motif and a β-Galp terminal unit are characteristic of Trypanosoma cruzi mucins.•The model 6-aminohexyl α-d-Galp(1 → 3)-[β-d-Galp(1 → 6)]-d-Galp was synthesized•Sialylation by T. cruzi trans-sialidase occurs at O-3 of the β-d-Galp unit.•HPAEC was used to follow sialylation with sialyllactose as donor.•The trisaccharide and the tetrasaccharide are tools for immunological studies.</description><identifier>ISSN: 0008-6215</identifier><identifier>EISSN: 1873-426X</identifier><identifier>DOI: 10.1016/j.carres.2017.08.007</identifier><identifier>PMID: 28858610</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Anti α-gal ; Antibodies - chemistry ; Antibodies - immunology ; Calcium-Binding Proteins - immunology ; Carbohydrate Sequence ; Chemistry Techniques, Synthetic ; Glycoproteins - metabolism ; Monosaccharide Transport Proteins - immunology ; Neuraminidase - metabolism ; Periplasmic Binding Proteins - immunology ; Trans-sialidase ; Trisaccharides - chemical synthesis ; Trisaccharides - metabolism ; Trypanosoma cruzi ; Trypanosoma cruzi - metabolism</subject><ispartof>Carbohydrate research, 2017-10, Vol.450, p.30-37</ispartof><rights>2017 Elsevier Ltd</rights><rights>Copyright © 2017 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-cc72870a78e5ca473695582ad6a7483000cf3afe160d5de7e1b764df84e8c8953</citedby><cites>FETCH-LOGICAL-c362t-cc72870a78e5ca473695582ad6a7483000cf3afe160d5de7e1b764df84e8c8953</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.carres.2017.08.007$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28858610$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Giorgi, M. Eugenia</creatorcontrib><creatorcontrib>Lopez, Rosana</creatorcontrib><creatorcontrib>Agusti, Rosalia</creatorcontrib><creatorcontrib>Marino, Carla</creatorcontrib><creatorcontrib>de Lederkremer, Rosa M.</creatorcontrib><title>Synthesis of a model trisaccharide for studying the interplay between the anti α-Gal antibody and the trans-sialidase reactions in Trypanosoma cruzi</title><title>Carbohydrate research</title><addtitle>Carbohydr Res</addtitle><description>Trypanosoma cruzi, the etiologic agent of Chagas disease, is covered by a dense glycocalix mainly composed by glycoproteins called mucins which are also the acceptors of sialic acid in a reaction catalyzed by a trans-sialidase (TcTS). Sialylation of trypomastigote mucins protects the parasite from lysis by the anti α-Galp antibodies from serum. The TcTS is essential for the infection process since T. cruzi is unable to biosynthesize sialic acid. The enzyme specifically transfers it from a terminal β-d-Galp unit in the host glycoconjugate to terminal β-d-Galp units in the parasite mucins to construct the d-NeuNAc(α2→3)β-d-Galp motif. On the other hand, although galactose is the most abundant sugar in mucins of both, the infective trypomastigotes and the insect stage epimastigotes, α-d-Galp is only present in the infective stage whereas β-d-Galf is characteristic of the epimastigote stage of the less virulent strains. Neither α-d-Galp nor d-Galf is acceptor of sialic acid. In the mucins, some of the oligosaccharides are branched with terminal β-d-Galp units to be able to accept sialic acid in the TcTS reaction. Based on previous reports showing that anti α-Galp antibodies only partially colocalize with sialic acid, we have undertaken the synthesis of the trisaccharide α-d-Galp(1→3)-[β-d-Galp(1→6)]-d-Galp, the smallest structure containing both, the antigenic d-Galp(α1→3)-d-Galp unit and the sialic acid-acceptor β-d-Galp unit. The trisaccharide was obtained as the 6-aminohexyl glycoside to facilitate further conjugation for biochemical studies. The synthetic approach involved the α-galactosylation at O-4 of a suitable precursor of the reducing end, followed by β-galactosylation at O-6 of the same precursor and introduction of the 6-aminohexyl aglycone. The fully deprotected trisaccharide was successfully sialylated by TcTS using either 3′-sialyllactose or fetuin as donors. The product, 6-aminohexyl α-d-NeuNAc(2→3)-β-d-Galp(1→6)-[α-d-Galp(1→3)]-β-d-Galp, was purified and characterized. [Display omitted] •The α-Gal (1–3)Gal motif and a β-Galp terminal unit are characteristic of Trypanosoma cruzi mucins.•The model 6-aminohexyl α-d-Galp(1 → 3)-[β-d-Galp(1 → 6)]-d-Galp was synthesized•Sialylation by T. cruzi trans-sialidase occurs at O-3 of the β-d-Galp unit.•HPAEC was used to follow sialylation with sialyllactose as donor.•The trisaccharide and the tetrasaccharide are tools for immunological studies.</description><subject>Anti α-gal</subject><subject>Antibodies - chemistry</subject><subject>Antibodies - immunology</subject><subject>Calcium-Binding Proteins - immunology</subject><subject>Carbohydrate Sequence</subject><subject>Chemistry Techniques, Synthetic</subject><subject>Glycoproteins - metabolism</subject><subject>Monosaccharide Transport Proteins - immunology</subject><subject>Neuraminidase - metabolism</subject><subject>Periplasmic Binding Proteins - immunology</subject><subject>Trans-sialidase</subject><subject>Trisaccharides - chemical synthesis</subject><subject>Trisaccharides - metabolism</subject><subject>Trypanosoma cruzi</subject><subject>Trypanosoma cruzi - metabolism</subject><issn>0008-6215</issn><issn>1873-426X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1uFDEMgEcIRJfCGyCUI5cZkvlJshckVEFBqsSBInGLvImHZjWTLHGmaHgPHoQX4ZlIdwtHTraTz7asr6qeC94ILuSrfWMhJaSm5UI1XDecqwfVRmjV1X0rvzysNpxzXctWDGfVE6J9KblU8nF11mo9aCn4pvr5aQ35BskTiyMDNkeHE8vJE1h7A8k7ZGNMjPLiVh--sgIzHzKmwwQr22H-jhiOrxCyZ79_1ZcwHfNddGtJ3PEzJwhUk4fJOyBkCcFmHwOVYew6rQcIkeIMzKblh39aPRphInx2H8-rz-_eXl-8r68-Xn64eHNV2062ubZWtVpxUBoHC73q5HYYdAtOgup1V861YwcjCsnd4FCh2CnZu1H3qK3eDt159fI095DitwUpm9mTxWmCgHEhI7Z9J4Xu1Lag_Qm1KRIlHM0h-RnSagQ3d0LM3pyEmDshhmtThJS2F_cblt2M7l_TXwMFeH0CsNx56zEZsh6DRecT2mxc9P_f8AcFjKI2</recordid><startdate>20171010</startdate><enddate>20171010</enddate><creator>Giorgi, M. 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Eugenia</creatorcontrib><creatorcontrib>Lopez, Rosana</creatorcontrib><creatorcontrib>Agusti, Rosalia</creatorcontrib><creatorcontrib>Marino, Carla</creatorcontrib><creatorcontrib>de Lederkremer, Rosa M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Carbohydrate research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Giorgi, M. Eugenia</au><au>Lopez, Rosana</au><au>Agusti, Rosalia</au><au>Marino, Carla</au><au>de Lederkremer, Rosa M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis of a model trisaccharide for studying the interplay between the anti α-Gal antibody and the trans-sialidase reactions in Trypanosoma cruzi</atitle><jtitle>Carbohydrate research</jtitle><addtitle>Carbohydr Res</addtitle><date>2017-10-10</date><risdate>2017</risdate><volume>450</volume><spage>30</spage><epage>37</epage><pages>30-37</pages><issn>0008-6215</issn><eissn>1873-426X</eissn><abstract>Trypanosoma cruzi, the etiologic agent of Chagas disease, is covered by a dense glycocalix mainly composed by glycoproteins called mucins which are also the acceptors of sialic acid in a reaction catalyzed by a trans-sialidase (TcTS). Sialylation of trypomastigote mucins protects the parasite from lysis by the anti α-Galp antibodies from serum. The TcTS is essential for the infection process since T. cruzi is unable to biosynthesize sialic acid. The enzyme specifically transfers it from a terminal β-d-Galp unit in the host glycoconjugate to terminal β-d-Galp units in the parasite mucins to construct the d-NeuNAc(α2→3)β-d-Galp motif. On the other hand, although galactose is the most abundant sugar in mucins of both, the infective trypomastigotes and the insect stage epimastigotes, α-d-Galp is only present in the infective stage whereas β-d-Galf is characteristic of the epimastigote stage of the less virulent strains. Neither α-d-Galp nor d-Galf is acceptor of sialic acid. In the mucins, some of the oligosaccharides are branched with terminal β-d-Galp units to be able to accept sialic acid in the TcTS reaction. Based on previous reports showing that anti α-Galp antibodies only partially colocalize with sialic acid, we have undertaken the synthesis of the trisaccharide α-d-Galp(1→3)-[β-d-Galp(1→6)]-d-Galp, the smallest structure containing both, the antigenic d-Galp(α1→3)-d-Galp unit and the sialic acid-acceptor β-d-Galp unit. The trisaccharide was obtained as the 6-aminohexyl glycoside to facilitate further conjugation for biochemical studies. The synthetic approach involved the α-galactosylation at O-4 of a suitable precursor of the reducing end, followed by β-galactosylation at O-6 of the same precursor and introduction of the 6-aminohexyl aglycone. The fully deprotected trisaccharide was successfully sialylated by TcTS using either 3′-sialyllactose or fetuin as donors. The product, 6-aminohexyl α-d-NeuNAc(2→3)-β-d-Galp(1→6)-[α-d-Galp(1→3)]-β-d-Galp, was purified and characterized. [Display omitted] •The α-Gal (1–3)Gal motif and a β-Galp terminal unit are characteristic of Trypanosoma cruzi mucins.•The model 6-aminohexyl α-d-Galp(1 → 3)-[β-d-Galp(1 → 6)]-d-Galp was synthesized•Sialylation by T. cruzi trans-sialidase occurs at O-3 of the β-d-Galp unit.•HPAEC was used to follow sialylation with sialyllactose as donor.•The trisaccharide and the tetrasaccharide are tools for immunological studies.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>28858610</pmid><doi>10.1016/j.carres.2017.08.007</doi><tpages>8</tpages></addata></record>
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subjects Anti α-gal
Antibodies - chemistry
Antibodies - immunology
Calcium-Binding Proteins - immunology
Carbohydrate Sequence
Chemistry Techniques, Synthetic
Glycoproteins - metabolism
Monosaccharide Transport Proteins - immunology
Neuraminidase - metabolism
Periplasmic Binding Proteins - immunology
Trans-sialidase
Trisaccharides - chemical synthesis
Trisaccharides - metabolism
Trypanosoma cruzi
Trypanosoma cruzi - metabolism
title Synthesis of a model trisaccharide for studying the interplay between the anti α-Gal antibody and the trans-sialidase reactions in Trypanosoma cruzi
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