Abstract
A new hishly potent, receptor-selective and prolonged-acting cyclic lactam analogue of α-melanotropin (α-MSH) has been designed and synthesized. Molecular dynamics simulations and molecular mechanics calculations were used in conjunction with results from previous conformational structure-biological activity studies to design a new class of linear and cyclic α-melanotropin (α-MSH) analogues. Examination of these properties of α-MSH and [Nle4,D-Phe7] α-MSH led to the design of the potent linear fragment analogue Ac-[Nle4,Asp5,D-Phe7,Lys10]α-MSH4-10-NH2, in which the Gly10 residue of α-MSH4-10 was replaced by Lys10 as the major novel change from previous investigations. This in turn led to the synthesis of the cyclic lactam analogue Ac-[Nle4,Asp5,D-Phe7,Lys10]α-MSH4-10-NH2, which was exceptionally potent in the lizard skin (90 times that of α-MSH) and mammalian melanoma tyrosinase (100 times that of α-MSH) assays and in addition exhibited prolonged biological activity.
Original language | English (US) |
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Pages (from-to) | 3413-3416 |
Number of pages | 4 |
Journal | Journal of the American Chemical Society |
Volume | 111 |
Issue number | 9 |
DOIs | |
State | Published - Apr 1989 |
Externally published | Yes |
ASJC Scopus subject areas
- Catalysis
- General Chemistry
- Biochemistry
- Colloid and Surface Chemistry