Synthesis and activity of NAcSerAspLysPro analogues on cellular interactions between T-cell and erythrocytes in rosette formation.
Analogues of NAcSerAspLysPro (AcSDKP), a natural regulator of hematopoiesis isolated from fetal calf bone marrow, were synthesized. The biological activity of these molecules were evaluated in vitro in the rosette assay, which measures the interaction between human Jurkat T-cells and sheep red blood cells. In this test, the tripeptide SerAspLys was the most efficient. Inhibitory activity was detected at the concentration 10(-14) M for the analogue and at 10(-9) M for the parent tetrapeptide. The dipeptide NAcSerAsp still showed activity but at much higher doses (10(-6) M). Substitution of polar amino acids led mostly to inactive molecules. Thus, replacement of Ser by Ala, or Lys by Orn yielded completely inactive compounds and replacement of Asp by Glu decreased the activity (10(-6) M). The present study gives an insight into the role of individual amino acids of AcSDKP in the inhibition of the rosette formation which implicates interactions with T-cell CD2 glycoprotein.
Thierry
J
J
Institut de Chimie des Substances Naturelles, CNRS 91198 Gif-sur-Yvette, France.
Papet
M P
MP
Saez-Servent
N
N
Plissonneau-Haumont
J
J
Potier
P
P
Lenfant
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001681:Biological Assay; D055598:Chemical Phenomena; D002621:Chemistry; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology*; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D008223:Lymphoma; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D012397:Rosette Formation; D012756:Sheep; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured
D009842:Oligopeptides; C058504:goralatide