ABSTRACT
The synthetic laminin pentapeptide amide fragment (LF), Tyr-Ile-Gly-Ser-Arg-NH2 corresponding to a part of B1 chain of the glycoprotein, laminin, and six of its analogues having structural modifications at positions 1, 3 and 4 were synthesized by solid phase method employing mainly 9-fluorenylmethoxycarbonyl-amino acid trichlorophenyl esters as coupling agents and Merrifield resin as the solid support. Their biological activities were studied in vivo by lung tumor colonization assay and in vitro by cell adhesion assay. The activity of synthetic LF was found to correlate with the earlier reported results in both in vivo and in vitro assays. Among the analogues made, [Tyr4] LF and [Thr4]LF were found to inhibit the lung tumor colonies more efficiently than LF itself in the in vivo assay whereas [D- Ser4]LF exhibited almost the same inhibition as LF.
Subject(s)
Animals , Antineoplastic Agents/pharmacology , Laminin/chemistry , Mice , Mice, Inbred C57BL , Oligopeptides/pharmacology , Peptides/pharmacologyABSTRACT
The delta-receptor selective dermorphin gen associated peptide (DGAP) and five of its analogues having structural modifications at positions 2, 4 and 5 were synthesized by the solid phase method using 9-fluorenylmethoxycarbonyl amino acid trichlorophenyl esters as coupling agents and rho-benzyloxybenzyl alcohol resin as the solid support. The delta-receptor selectivity of these peptides was determined by guinea pig ileum and mouse vas deferens assays. The latter assay was carried out using modified Kreb's solution aerated with pure oxygen instead of carbogen. All the synthetic peptides were found to be delta-receptor selective.
Subject(s)
Amino Acid Sequence , Animals , Biological Assay , Guinea Pigs , Male , Mice , Molecular Sequence Data , Oligopeptides/chemical synthesis , Peptides/chemical synthesis , Receptors, Opioid, delta/antagonists & inhibitorsABSTRACT
Using mainly 9-fluorenylmethyloxycarbonyl amino acid 2, 4, 5-trichlorophenyl esters in the presence of 1-hydroxybenzotriazole and the solid support p-alkoxybenzyl alcohol resin, synthesis of luteinizing hormone releasing hormone analogues was carried out with minimal side-chain protection. Catalytic transfer hydrogenation was employed for removal of NO2 and Z-groups from Arg and < Glu respectively avoiding the use of HF and this led to good yields. An aromatic, hydrophilic amino acid, D-(p-hydroxyphenyl) glycine was incorporated into luteinizing hormone releasing hormone molecule along with other modifications. The agonistic as well as antagonistic activities of all the peptides have been studied.
ABSTRACT
Nine analogues of the opioid pentapeptides leucine-/ methionine-enkephalinamide, involving replacement of amino acid at position 5 or amino acids at positions 2 and 5, have been synthesized by the solid phase method using mainly 9-fluorenylmethyloxycarbonyl amino acid trichlorophenyl esters in the presence of 1-hydroxybenzotriazole, the solid support being the Merrifield resin. All the analogues were effective in inhibiting the electri cally stimulated contractions of the guinea pig ileum (in vitro) and one of them, tyrosyl-Dnorvalyl- glycyl-phenylalanyl-methioninamide was found to be about 82 times more active than morphine. They also exhibited analgesic activity as well as antidiarrhoeal activity in mice (in vivo).
ABSTRACT
The opioid pentapeptide leucine-enkephalinamide and eleven of its analogues have been synthesised by the solid phase technique employing mostly 9-fluoroenylmethyloxycarbonyl amino acid active esters in the presence of 1-hydroxybenzotriazole. Both the conventional chloromethylated copolystyrene-2% divinylbenzene resin as well as p-alkoxybenzyl alcohol resin were employed and it was observed that yields were uniformly better with the latter resin. The analogues were made by affecting single or multiple replacements of amino acids involving positions 1,2 and 5. Some of the analogues were found to be more potent than morphine in the guinea pig ileum assay.