84588-89-6

Usage

InChI:InChI=1/C23H36N6O11S/c24-8-2-1-3-13(23(39)40)27-22(38)15(10-41)29-21(37)14(9-18(33)34)28-20(36)12(5-7-17(31)32)26-19(35)11-4-6-16(30)25-11/h11-15,41H,1-10,24H2,(H,25,30)(H,26,35)(H,27,38)(H,28,36)(H,29,37)(H,31,32)(H,33,34)(H,39,40)/t11-,12-,13-,14-,15-/m0/s1

Upstream product

• 141451-02-7 Glp-Glu-Asp-Cys(Acm)-Lys-OH 
• 166267-91-0 Glp-Glu(OBzl)-Asp(OBzl)-Cys(Acm)-Lys(Z)-OBzl 
• 115150-61-3 2 

Relevant academic research and scientific papers

The hemoregulatory peptide pEEDCK may inhibit stem cell proliferation via hydropathic binding to antisense sequence motifs in interleukin-11 and other growth factors

In undisturbed bone marrow, most hemopoietic stem cells are nonproliferating despite the presence of multiple growth factors. Endogenous inhibitory factors are responsible for maintenance of this quiescence. Previously we sequenced and synthesized the inhibitory pentapeptide pGlu-Glu- Asp-Cys-Lys (pEEDCK), which originally derives from granulocytes, and investigated the role of this peptide in stem cell quiescence. To provide some mechanistic insight, in the present work we studied the structural relationship of this peptide to specific growth-factor-derived sequence motifs. In the murine system in vivo as well as in long-term bone marrow, antiserum to pEEDCK produced a significant stimulation of formation of colony-forming units-granulocyte/macrophage. Binding of peptides to proteins often takes place at hydropathically complementary sites. Therefore, we searched for peptides corresponding to the complementary sequence to pEEDCK. We identified antisense sequences in the genes of various cytokines and cytokine receptors including interleukin-11. The corresponding peptide Val- Leu-Leu-Thre-Arg (VLLTR) and several other peptides hydropathically complementary to pEEDCK were synthesized. We found that pEEDCK binds specifically to these peptides as well as to complete interleukin-11. Dissociation constants were in the 10 μM range. The peptide hydropathically corresponding to pEEDCK (VLLTR) was found to stimulate colony-forming units- granulocyte/macrophage formation. Our data suggest that pEEDCK could exert a coordinating function in the hemopoietic cytokine network by binding to multiple regulatory proteins and modulating their activity.

Granulopoiesis Inhibiting Factor: Synthesis and Biological Activity

Three schemes of synthesis for pentapeptide Glp-Glu-Asp-Cys-Lys-OH were compared.Acetamidomethyl protection was used for the mercapto group of cysteine.For the same purpose, cystine was used as the starting compound for synthesis.The optimal method was shown to be the solid phase method with S-acetamidomethyl cysteine protection that can be removed by mercuric acetate before the cleavage of a peptide from a polymer.The stabilized peptide inhibits proliferation of bone marrow cells of patients with chronic myeloleukemia 5- to 20-fold and has a less pronounced effect (up to 2-fold inhibition) on peripheral blood cells.Thus, its application for the therapy of hemoblastoses is promising. Key words: granulopoiesis inhibiting factor, solid phase peptide synthesis, cysteine-containing pentapeptide

Peptide compounds

The invention provides compounds of the general formula: STR1 (in which R1 is the residue of glycine or D-alanine, and all other amino-acid residues are in the L-form, X1 and X2, which may be the same or different, are OH or NH2 and n is 0 or 1) and their physiologically acceptable salts. The compounds of the invention are capable of inhibiting the myelopoietic system of humans and animals, thereby protecting said system against attack by cytotoxic drugs.