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 specificity of this action was investigated using a number of peptide analogues of AcSDKP and evaluating their ability to "block" the recruitment of a primitive murine hematopoietic precursor (high proliferative potential 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 proliferation stimulator was not evident for either AcSDDKP or AcSD beta KP, two structurally distinct forms of the molecule; similar no stimulator-"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 action of AcSDKP is specific and that the tripeptide sequence SDK may be a significant component of the molecule.