Studies on the structure-activity relationship of delta-sleep inducing peptide

DSIP and its fourteen analogs as well as three short peptides were synthesized by solid phase method. The design of the analogs was based on the consideration of the introduction of D-amino acid into the molecules to inhibit the enzymatic hydrolysis and the introduction of amino acids with a hydrophobic side chain. The modification was placed on the position of 1, 3, 4, 5, 8 and 9, e.g. D- Trp1, Tyr1, Tyr1 Phe5, D-Trp1 Phe8, Trp3,4, D-Trp1,3,4 Phe8, D-Trp3,4 Phe8 D-Glu9, D-pF-Phe3,4 Phe8 D-Glu9, Phe5, Glu5 Asp9, Tyr6 Asp9, Asp9 and Ala7-DSIP as well as Trp-Ala-Gly-Gly-Asp, Trp-Ala-Gly-Gly-Glu and Trp-Gly-Glu. DSIP and Phe5-DSIP were also prepared by pentafluorophenyl ester method. The purity of the synthetic peptides was checked by amino acid analysis, elemental analysis, thin layer chromatography and paper electrophoresis. The biological assay showed that the analogs of D-Trp1, Tyr1, Tyr1 Phe5 and Ala7-DSIP as well as three short peptides were inactive whereas Phe5-DSIP showed similar activity as that of synthetic DSIP.