Solid phase synthesis of glycopeptide dendrimers with Tn antigenic structure and their biological activities. Part I
✍ Scribed by Jan Ježek; Jiří Velek; Pavel Vepřek; Vlasta Velková; Tomáš Trnka; Jaroslav Pecka; Miroslav Ledvina; Jiří Vondrášek; Martin Písačka
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 225 KB
- Volume
- 5
- Category
- Article
- ISSN
- 1075-2617
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✦ Synopsis
Multiple antigenic peptides containing dimeric Tn antigen [Ac-(Tn) 2 -k-Abu] 4 -(Lys-X) 2 -Lys-i-Ala (V: X= 0; VIII: X= k-Abu) and [Ac-(Tn) 2 -k-Abu] 8 -(Lys-X) 4 -(Lys-X) 2 -Lys-i-Ala (XI: X=0; XIV: X=k-Abu), immobilized on biocompatible Tenta Gel S NH 2 support were prepared by SPPS. Rosetting tests of V, VIII, XI and XIV showed positive reactions with anti-Tn (DAKO) and Tn+ erythrocytes, with anti-Tn/A (BRIC 66) and Tn+ and A erythrocytes, other combinations were negative. In all the animals immunized with XIV, we found a remarkable increase in the level of anti-Tn (titre 2000 -64000, score 105 -167) and no change of anti-A levels (titre 8, score 13-17). Neither non-immune nor immune sera showed any reactivity with T + , Cad + and blood group O erythrocytes. Immunized mice did not exhibit any sign of adverse reaction to the administered conjugates. Biological activities were correlated with molecular modelling and molecular dynamic calculations. The biological activities of these synthetic Tn antigen conjugates (good availability for the immunological interactions, highly specific immunogenicity, good biological tolerance) together with their precise chemical characterization seem to be a promising approach to preparation of anti-tumour vaccine and affinity purification of anti-Tn antibodies.