THE MOLECULAR SPECIFICITY OF ACTION OF THE TETRAPEPTIDE ACETYL-N-SER-ASP-LYS-PRO (ACSDKP) IN THE CONTROL OF HEMATOPOIETIC STEM-CELL PROLIFERATION

The hemoregulatory tetrapeptide Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP, M(r) = 487 amu) prevents the recruitment of hematopoietic stem cells into S phase. AcSDKP does not possess inherent inhibitory activity against hematopoietic stem cells, rather it appears to act by ''blocking'' the action of a hematopoietic stem cell proliferation stimulator present in extracts of regenerating hematopoietic tissue. The molecular specif icity of this action was investigated using a number of peptide analog ues of AcSDKP and evaluating their ability to ''block'' the recruitmen t of a primitive murine hematopoietic precursor (high proliferative po tential colony forming cell HPP-CFC) into S phase following incubation with a hematopoietic stem cell proliferation stimulator. The capacity of AcSDKP to compromise the action of the hematopoietic stem cell pro liferation stimulator was not evident for either AcS(D)DKP or AcSD(bet a)KP, two structurally distinct forms of the molecule; similarly no st imulator-''blocking'' activity was observed for the tripeptide Ala-Asp -Lys (ADK, M(r) = 332 amu), while the tripeptide Ser-Asp-Lys (SDK, M(r ) = 348 amu) was active. It would appear that the hemoregulatory actio n of AcSDKP is specific and that the tripeptide sequence SDK may be a significant component of the molecule.