| Summary: | 博士 === 中國醫藥學院 === 藥物化學研究所 === 88 === In my search for novel inhibitors of methionine S-adenosyl transferase（MAT）and potentiators of the activity of retinoic acid in inducing differentiation of HL-60 cells. A series of HP analogues（HP1~12）were designed. The solid phase peptide synthetic procedure was adopted for the preparation of these target peptides. Preliminary tests of their inhibitory effects on the MAT of HL-60 cells was performed according to the surface plasmon resonance（SPR）technology. Results indicate that PyroGlu-Glu-Glu-Cys-Lys-OH (HP1) and PyroGlu-Asp-Asp-Cys-Lys-OH(HP3) ,both being natural HP, displayed significant inhibitory effects. The synthetic HP6, obtained by converting the C-terminal-COOH of HP1 to-CONH2, demonstrated improved activity over HP1.
After testing the target peptides on HL-60 cells for differentiation and proliferation capability, a preliminary SAR was established.
All of the peptides (HP1~12) showed significant activity. Among them, PaA-Glu-Glu-Cys-Lys-NH2 (HP12) exhibited the highest activity with about 50 times the potency of phenylacetic acid in the potentiating activity of retinoic acid to induce cell differentiation.
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