Sialyl Tn

In order to obtain the biologically interesting sialyl TN antigen glyco-peptides, 7V-(benzyloxycarbonyl)-C -[methyl(5-acetamido-4s7,8,9-tetra-C -acetyl-3,5-dideoxy-D-g/ycmM -D-gtf/0cfo-2-nonulopyranosyl)-onate-(2 — ... 

Independently and at the same time the incorporation of a sialyl-TN-antigen building block in the synthesis of a fragment from the HIV gpl20 glycoprotein was described.41... 

Scheme 21 Synthesis of the 2,6-Sialyl TN-Antigen Building Block Using a Sialyl Donor without a C3 Participating Group[125l...

Biotinylated sialyl Tn antigen with PAA backbone (Sialyl Tn Neu5Aca2-6GalNAca-PAA-biotin, Glycotech). 

Fig. 1. An analysis procedure of a ptiotocrosslinked sugar an ay by SPR imaging. A fabricated sugar array with sialyl T, sialyl Tn and sialyl LacNAc were exposed with MAFI, regenerated with NaOFI and then, exposed with SA and anti-SA.

G. D. MacLean, M. Reddish, R. R. Koganty, T. Wang, S. Ganchi, M. Smolensk), J. Samuel, J. M. Nabholtz, and B. M. Longenecker, Immunization of breast cancer patients using a synthetic sialyl-Tn glycoconjugate plus Delox adjuvant, Cancer Immunol. Immunother, 36 215 (1993). 

Cho, S. H., Hortobagyi, G. N., Hittleman, W. N., and Dhingra, K. 1994. Sialyl-Tn antigen expression occurs early during human mammary carcinogenesis and is associated with high nuclear grade and aneuploidy. Cancer Res. 54 6302-6305. 

Davidson, B., Berner, A., Nesland, J. M., Risberg, B., Kristensen, G. B., Trope, C. G., and Bryne, M. 2000. Carbohydrate antigen expression in primary tumors, metastatic lesions, and serous effusions from patients diagnosed with epithelial ovarian carcinoma Evidence of up-regulated Tn and Sialyl Tn antigen expression in effusions. Hum. Pathol. 37 1081-1087. 

Liebe, B. and Kunz, H. (1997) Solid-phase synthesis of a tumor-associated sialyl-TN antigen glycopeptide with a partial sequence of the tandem repeat of the MUC-1 mucin. Angew. Chem. Int. Ed. 36, 618-621. 

Endo T, Koizumi S, Tabata K, Kakita S, Ozaki A. Large-scale production of the carbohydrate portion of the sialyl-Tn epitope, a-Neup5Ac-(2- 6)-D-GalpNAc, through bacterial coupling. Carbohydr. Res. 2001 330 439-443. 

The hrst synthesis of the sialyl Tn antigen was reported by Ogawa et al. and involved the synthesis of a disaccharide donor consisting of an anomeric trichloroacetimidate of a-NeuNAc-(2 6)-a-D-GalNAc [135]. The donor was then used in glycosylation of Af-(benzyloxycarbonyl)-L-serine... 

SCHEME Synthesis of sialyl-Tn antigen building blocks by sialylation of the Tn antigen building... 

SCHEME 1 S.26 Enzymatic sialylations of the mucin-type Tn and T antigen glycopeptides 199 and 201 gave glycopeptides 200, 202 and 203 which contained the sialyl-Tn and the sialyl-T antigens. 

Elofsson, M, Salvador, L A, Kihlherg, J, Preparation of Tn and sialyl Tn building blocks used in Fmoc solid-phase synthesis of glycopeptide fragments from HIV gpl20. Tetrahedron, 53, 369-390, 1997. 

Liebe, B, Kunz, H, Solid-phase synthesis of a sialyl-Tn-glycoundecapeptide of the MUCl Repeating Unit, Helv. Chim. Acta, 80, 1473-1482, 1997. 

Nakahara et al. accomplished an early s)uithesis of a trimeric a2-6 sialyl-TN glycopeptide. The resultant glycopeptide corresponds to a partial structure of glycophorin A [103] (O Scheme 19). 

Liebe and Kunz made further use of the HYCRON linker methodology in the construction of the a2-6 sialyl-TN antigen attached to a portion of the mucin MUCl repeat peptide [104] (O Scheme 20). 

Danishefsky s laboratory has recently reported syntheses of the clustered motif of both the a2-6-sialyl-TN and a2-6 sialyl-T antigens (O Fig. 6) using a similar procedure to that described for the clustered T antigen described above [105,106]. Conjugation and immunological evaluation of these constructs is currently in progress. 

---