Abstract
A new highly 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,Lys 10]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,Lys 10]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) |
|---|---|
| Pages (from-to) | 3413-3416 |
| Number of pages | 4 |
| Journal | Journal of the American Chemical Society |
| Volume | 111 |
| Issue number | 9 |
| State | Published - 1989 |
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ASJC Scopus subject areas
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Design of a new class of superpotent cyclic α-melanotropins based on quenched dynamic simulations. / Al-Obeidi, Fahad; Hruby, Victor J; Pettitt, B. Montgomery; Hruby, Victor J.
In: Journal of the American Chemical Society, Vol. 111, No. 9, 1989, p. 3413-3416.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Design of a new class of superpotent cyclic α-melanotropins based on quenched dynamic simulations
AU - Al-Obeidi, Fahad
AU - Hruby, Victor J
AU - Pettitt, B. Montgomery
AU - Hruby, Victor J.
PY - 1989
Y1 - 1989
N2 - A new highly 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,Lys 10]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,Lys 10]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.
AB - A new highly 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,Lys 10]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,Lys 10]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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0024551431&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:0024551431
VL - 111
SP - 3413
EP - 3416
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 9
ER -