In vitro effect of acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) analogs resistant to angiotensin I-converting enzyme on hematopoietic stem cell and progenitor cell proliferation
S. Gaudron et al., In vitro effect of acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) analogs resistant to angiotensin I-converting enzyme on hematopoietic stem cell and progenitor cell proliferation, STEM CELLS, 17(2), 1999, pp. 100-106
The tetrapeptide Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP), an inhibitor of hematop
oietic stem cell proliferation, is known to reduce in vivo the damage resul
ting from treatment with chemotherapeutic agents or ionizing radiation on t
he stem cell compartment, Recently, AcSDKP has been shown to be a physiolog
ical substrate of the N-active site of angiotensin I-converting enzyme (ACE
), Four analogs of the tetrapeptide expressing a high stability towards ACE
degradation in vitro have been synthesized in order to provide new molecul
es likely to improve the myeloprotection displayed by AcSDKP, These analogs
are three pseudopeptides with a modified peptidic bond, Ac-Ser Psi(CH2-NH)
Asp-Lys-Pro, Ac-Ser-Asp-Psi(CH2-NH)Lys-Pro, Ac-Ser-Asp-Lys Psi(CH2-N)Pro, a
nd one C-terminus modified peptide (AcSDKP-NH2), We report here that these
analogs reduce in vitro the proportion of murine colony-forming units-granu
locyte/macrophage in S-phase and inhibit the entry into cycle of high proli
ferative potential colony-forming cells, The efficacy of AcSDKP analogs in
preventing in vitro primitive hematopoietic stem cells from entering into c
ycle suggests that these molecules could be new candidates for the powerful
inhibition of hematopoietic stem and progenitor cell proliferation in vivo
.