Immunomodulatory effect of synthetic branched polypeptides. II.

A comparative investigation of various polypeptides was carried out in order to elucidate structure-activity correlations. The immunoadjuvant properties of the chemically well-characterized branched polypeptides, poly[Lys-(DL-Alam)] (Lys:Ala = 1:2.95) (AK), poly[Lys-(D-Leui-DL-Alam)] (Lys:Ala:Leu = 1:3.0:0.95) (D-LAK), and poly[Lys-Hisi-DL-Alam)] (Lys:Ala:His = 1:2.95:0.85) (HAK), were investigated. D-LAK and HAK were able to augment the antibody response of BDF inbred mice to immunization with sheep red blood cells (SRBC), as assessed by the hemolytic plaque-forming cell assay, whereas AK had no similar effect. The stimulating effect of D-LAK and HAK was dependent on dose and timing of treatment relative to SRBC immunization. However, the optimal dose levels were lower and the effective dose interval more restricted as compared to the previously described poly[Lys-(Leui-DL-Alam)] (LAK). Like LAK, both HAK and D-LAK were able to compensate for the immunosuppressive effect of the cytotoxic drugs dianhydrogalactitol, vincristine, and 5-fluorouracil, which all have different mechanisms of action, provided that combined treatment by polypeptide and drug was applied repeatedly before the SRBC immunization.