Solid phase synthesis of glycopeptide dendrimers with Tn antigenic structure and their biological activities. Part I

Multiple antigenic peptides containing dimeric Tn antigen [Ac-(Tn)(2)-gamma -Abu)(4)-(Lys-X)(2)-Lys-beta-Ala (V: X=0; MI: X= gamma-Abu) and [Ac-(Tn)(2) -gamma-Abu)(8)-(Lys-X)(4)-(Lys-X)(2)-Lys-beta-Ala (XI: X= 0; XI: X= gamma-A bu), immobilized on biocompatible Tenta Gel S NH2 support were prepared by SPPS. Resetting 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 + a nd A erythrocytes, other combinations were negative. In all the animals imm unized with XIV, we found a remarkable increase in the level of anti-Tn (ti tre 2000-64000, score 105-167) and no change of anti-A levels (titre 8, sco re 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 activit ies were correlated with molecular modelling and molecular dynamic calculat ions. The biological activities of these synthetic Tn antigen conjugates (g ood availability for the immunological interactions, highly specific immuno genicity, good biological tolerance) together with their precise chemical c haracterization seem to be a promising approach to preparation of anti-tumo ur vaccine and affinity purification of anti-Tn antibodies. Copyright (C) 1 999 European Peptide Society and John Wiley & Sons, Ltd.