Pharmacological activities of some synthetic peptides related to dermorphin
Article
Sivanandaiah, KM, Suresh Babu, VV, Shankaramma, SC et al. (1997). Pharmacological activities of some synthetic peptides related to dermorphin
. 29(2), 92-98.
Sivanandaiah, KM, Suresh Babu, VV, Shankaramma, SC et al. (1997). Pharmacological activities of some synthetic peptides related to dermorphin
. 29(2), 92-98.
Objectives: To investigate the relationship between the structure of demorphins (DM) and their pharmacological properties, six analogues of [Hyp6]DM and [Pro6]DM were synthesised and their biological activities were studied. Methods: The peptides were synthesised by the solid phase method using 9-fluorenylmethoxycarbonyl amino acid trichlorophenyl esters as coupling agents and Merrifield resin as solid support. The opioid agonist activity was studied using co-axially, electrically stimulated contraction of isolated guinea pig ileum (GPI, in vitro). Their analgesic activity was assessed in mice using Eddy's hot plate method and tail-flick method. The antidiarrhoeal activity was determined by the charcoal meal test in mice. Results: In the GPI assay, the synthetic analogues possess agonistic activity that are less pronounced than morphine. Peptides I and II (substitution of ser of position 7 and Gly at position 4 in [Hyp6]DM series respectively) possessed considerable analgesic activity but are almost inactive in the GPI assay. Peptide III ([Pro6, Sar7]DM) possess only analgesic activity. In GPI assay, peptide IV was inactive. Peptide V and VI had equipotent analgesic and antidiarrhoeal activity. Conclusion: Peptides with various structures can possess specificities that may prove useful in biological applications. Among them [Sar4, Hyp6, Tyr7]DM, [Hyp6, Pro7]DM, [Pro6, Sar ]DM and [Phg3, Pro]DM exhibited a high degree of selectivity in their activities.
