The synthesis and in vitro pharmacological tests of 5 ketomethylene tetrapeptide analogues of the opioid heptapeptide dermorphin H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2 are described in this study. The substitution of the original Phe-Gly peptide bond (-CO-NH-) by the ketomethylene linkage (-CO-CH2-) provided analogues with reduced opioid activity.
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Ketomethylene and (cyanomethylene)amino pseudopeptide analogues of the C-terminal hexapeptide of neurotensin.
J Med Chem
March 1995
Instituto de Química Médica (CSIC), Madrid, Spain.
A series of pseudopeptide analogues of the C-terminal hexapeptide of neurotensin (NT8-13), namely [Tyr11 psi[COCH2]Phe12]-, [Ile12 psi[COCH2]Phe13]-, and [Tyr11 psi[CH(CN)NH]Ile12]NT8-13 with different stereochemistries, has been synthesized and evaluated for its potency in displacing labeled NT from rat cortex membranes. Ketomethylene pseudohexapeptides were prepared from the corresponding Boc-protected ketomethylene dipeptide derivatives, previously formed, using different solid phase synthesis (SPS) conditions, while (cyanomethylene)amino analogues were directly prepared by SPS using Fmoc strategy. H-Arg-Arg-Pro-Tyr psi[COCH2]-Phe-Leu-OH was nearly as potent as NT8-13 and [Phe12]NT8-13 in binding to the receptor.
View Article and Find Full Text PDFTwo pentapeptide analogues of the ketomethylene-containing angiotensin converting enzyme (ACE) inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline (1) were synthesized and evaluated as ACE inhibitors and antihypertensive agents. Compounds 14 and 15 were very potent ACE inhibitors with I50 values of 7.0 and 3.
View Article and Find Full Text PDFStructure-activity relationships of dermorphin tetrapeptides carrying a ketomethylene linkage.
Arzneimittelforschung
March 1986
The synthesis and in vitro pharmacological tests of 5 ketomethylene tetrapeptide analogues of the opioid heptapeptide dermorphin H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2 are described in this study. The substitution of the original Phe-Gly peptide bond (-CO-NH-) by the ketomethylene linkage (-CO-CH2-) provided analogues with reduced opioid activity.
View Article and Find Full Text PDFA peptide analogue of Leu-enkephalin was synthesized in which the amide linkages between Tyr-Gly and Gly-Gly were replaced by ketomethylene groups. The resulting analogue, 12, had 1/4000th and 1/2400th the opiate receptor binding activity of Leu-enkephalin when (3H) [D-Ala2,D-Leu5]enkephalin and (3H)naloxone, respectively, were used as tritiated ligands. When tested for analgesia in mice by the tail-flick assay, 12 produced analgesia in 50% of the mice tested at a dose of 24.
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