Synthesis and immunostimulating activity of a thioglycolipopeptide glycomimetic as a potential anticancer vaccine derived from Tn antigen1

Article abstract of DOI:10.1080/07328300008544097

The Tn epitope is one of the tumor associated O-linked cell surface glycopeptides. It is expressed in over 70% of human epithelial cancers such as lung, colon, stomach and breast carcinomas. The glycosidic linkage of the Tn antigen, between N-acetylgalactosamine and serine or threonine, can be cleaved either chemically or enzymatically in the presence of glycosidases. The latter case is particularly a problem in vivo. Therefore, it would be of great interest to obtain a metabolically stable analogue of the Tn antigen that maintains or improves the immunogenic activity of the latter. The purpose of this work was to synthesize a totally synthetic vaccine using a chemically and metabolically stable glycomimetic of the Tn antigen in which the interglycosidic oxygen was replaced by a sulphur atom (S-Tn). The S-Tn thioglycopeptide was linked to the P₃CS immunoadjuvant to obtain the potential S-Tn vaccine. Moreover, we synthesized the natural Tn antigen and derivatized it similarly to obtain the Tn vaccine. Last, we evaluated the immunostimulating activity of the two synthetic potential vaccines in vitro using cultured mouse splenocytes. The S-Tn construct showed immunostimulating activity comparable, in terms of maximal response, to the Tn analogue. Moreover, due to its higher stability the S-Tn construct reached its maximal effect at lower doses compared to the Tn analogue.

Full text of DOI:10.1080/07328300008544097

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Journal of Carbohydrate Chemistry
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Synthesis and Immunostimulating
Activity of A Thioglycolipopeptide
Glycomimetic As A Potential
Anticancer Vaccine Derived From Tn
Antigen
Ennio Bousquet , Angelo Spadaro , Maria S. Pappalardo ,
Renato Bernardini , Rosalba Romeo , Luigi Panza & Giuseppe
Ronsisvalle
a Department of Pharmaceutical Science , School of
Pharmacy
b Department of Pharmacology , School of Medicine
University of Catania , Viale Andrea Doria 6, 95125 Catania,
Italy
c Department of Chemical, Alimentary, Pharmaceutical and
Pharmacological Sciences , University of Eastern Piemonte
Viale Ferrucci , 33, 28100 Novara, Italy
Published online: 07 Mar 2008.
To cite this article: Ennio Bousquet , Angelo Spadaro , Maria S. Pappalardo , Renato
Bernardini , Rosalba Romeo , Luigi Panza & Giuseppe Ronsisvalle (2000) Synthesis and
Immunostimulating Activity of A Thioglycolipopeptide Glycomimetic As A Potential Anticancer
Vaccine Derived From Tn Antigen, Journal of Carbohydrate Chemistry, 19:4-5, 527-541, DOI:
10.1080/07328300008544097
To link to this article: http://dx.doi.org/10.1080/07328300008544097
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