Ac-SDKP peptide (also known as seraspenide or goralatide)

 The synthetic tetrapeptide Ac-SDKP, also called seraspenide or goralatide, has the chemical structure 1-(N2-(N-(N-acetyl-L-seryl)-L-alpha-aspartyl)-L-lysyl)-L-proline, the molecular formula C20H33N5O9, and a molecular weight of 487.50412 dalton. This tetrapeptide is involved in angiogenesis and the regulation of the immune response by blocking the proliferation of lymphocytes. It is generated by the cleavage of thymosine beta4 and inhibits the proliferation of hematopoietic stem cells and the proliferation and secretion of fibroblasts in the myocardium and the glomeruli. Lymphocytes are a type of white blood cells in the vertebrate immune system and are part of the adaptive immune system. The seraspenide peptide inhibits cell cycle entry of normal hematopoietic stem cells. Ac-SDKP protects hemopoiesis, the blood cell formation from established blood cell precursors, against damage caused by cytarabine, cyclophosphamide and carboplatin in mice. Hematopoietic stem cells give rise to all other blood cells. The renin–angiotensin system, a hormonal system that regulates blood pressure and water or fluid balance in mammals, is central to regulation of blood pressure and electrolyte homeostasis. N-Ac-Ser-Asp-Lys-Pro is an inhibitor of primitive hematopoietic cells and has been reported to block the proliferation of clonogenic cells freshly isolated from normal marrow and cord blood. Ac-SDKP can cause a transient decrease in nonadherent cell and progenitor output when added repeatedly to normal long-term marrow cultures. Ac-SDKP is detectable in experiments with marrow from patients with chronic myeloid leukemia. Clonogenic cells are cells that have the potential to proliferate and to give rise to a colony of cells. Only some daughter cells from each generation retain the potential to proliferate. The angiotensin-converting enzyme, a key protease, has a range of substrates, including N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP). The peptide Ac-SDKP is cleared almost exclusively by the angiotensin-converting enzyme. N-Acetyl-Ser-Asp-Lys-Pro is a negative regulator of haematopoietic stem cell differentiation and a potent antifibrotic agent. AZT (3'-azido-3'-deoxythymidine), the main antiviral drug used in AIDS treatment, is toxic to hematopoietic progenitor cells and is known to induce anemia, a decrease in number of red blood cells, and neutropenia, the abnormally low number of neutrophils or white blood cells. The tetrapeptide AcSerAspLysPro (AcSDKP, Seraspenide) has been shown to increase the survival of mice subjected to high doses of chemotherapy and to reversibly block the cycling of human granulocyte-macrophage colony forming unit and burst forming unit erythroid progenitors. Furthermore, it has been suggested that AcSDKP may be an efficient factor in preserving progenitors against AZT-induced hematopoietic toxicity. Research indicates that the peptide could protect hematopoietic stem cells during anti-neoplastic treatments leaving cancerous cells unprotected. The tetrapeptide opposes the effects of TGFbeta and could prevent fibrosis after myocardial infarcts and glomeruli fibrosis during the natural course of diabetic nephropathy.