Synthesis and biological evaluation of the superagonist [N alpha-chlorotriazinylaminofluorescein-Ser1,Nle4,D-Phe7]-al pha-MSH.
The fluorescein-labeled melanotropin [N alpha-chlorotriazinylaminofluorescein-Ser1,Nle4,D-Phe 7]-alpha-MSH, was prepared by solid-phase techniques of peptide synthesis. The biological actions of this analogue were determined in several melanocyte bioassays and were compared with the parent peptide [Nle4,D-Phe7]-alpha-MSH and the native hormone alpha-MSH. The fluorescein compound was a superpotent agonist with approximately 10 times more activity than alpha-MSH in both the frog and the lizard skin bioassays. Murine S91 melanoma cells assayed in vitro (tyrosinase bioassay) were as responsive to the fluorescein analogue as to alpha-MSH. The analogue exhibited ultraprolonged biological activity and the biological activities were unaffected by treatment of the analogue with alpha-chymotrypsin. The fluorescein-labeled melanotropin should prove useful for melanotropin receptor characterization.
Chaturvedi
D N
DN
Hruby
V J
VJ
Castrucci
A M
AM
Kreutzfeld
K L
KL
Hadley
M E
ME
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D019793:Fluorescein; D005452:Fluoresceins / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D008116:Lizards; D009074:Melanocyte-Stimulating Hormones / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008544:Melanocytes / Q000187:drug effects; D014442:Monophenol Monooxygenase / Q000378:metabolism; D011894:Rana pipiens; D011956:Receptors, Cell Surface / Q000502:physiology*; D011979:Receptors, Pituitary Hormone; D012867:Skin / Q000187:drug effects; D012880:Skin Pigmentation / Q000187:drug effects; D013997:Time Factors; D000521:alpha-MSH / Q000031:analogs & derivatives*
D005452:Fluoresceins; D011956:Receptors, Cell Surface; D011979:Receptors, Pituitary Hormone; D000521:alpha-MSH; C029446:MSH receptor; D009074:Melanocyte-Stimulating Hormones; C045810:MSH, N(alpha)-chlorotriazinylaminofluorescein-1-Ser-4-Nle-7-Phe-alpha-; D014442:Monophenol Monooxygenase; D019793:Fluorescein