| Popis: |
Leucosulfakinin and leucosulfakinin-II are sulfated insect neuropeptides with homology to human gastrin II and cholecystokinin. Biological evaluation of the analog [Ser(SO3H)2, Tyr5]leucosulfakinin-II, two cholecystokinin analogs containing key leucosulfakinin amino acid replacements, and a Tyr(SO3H) position-analog series has demonstrated that while the presence of a sulfate group is critical to leucosulfakinin myotropic activity, its position is not. Most strikingly, the analog [Tyr (SO3H)5,Phe6,Nle9]leucosulfakinin, in which the sulfate moiety is shifted one position towards the N-terminus relative to the parent peptide, retains a very significant 38% of the parent's threshold activity. A shift in the location of the sulfate group by two to five positions toward the N-terminus led to reduction of potency to a significant but low plateau of activity, whereas a shift by more than one position towards the C-terminus led to a complete loss of activity. The introduction of a single residue (Arg) in the 7 position of CCK-8 transforms this inactive mammalian hormone into a myotropically-active leucosulfakinin analog on the isolated cockroach hindgut. |
