NMR and quenched molecular dynamics studies of superpotent linear and cyclic alpha-melanotropins.
Conformational searching, computer simulations, synthesis and NMR are used on a variety of alpha melanocyte-stimulating hormone (alpha-MSH) analogues to understand the physical characteristics required for biological potency. Peptides I (Ac-[Nle4,Asp5,D-Phe7,Lys10]alpha-MSH(4-10)-NH2), II (Ac-c[Nle4,Asp5,D-Phe7,Lys10]alpha-MSH(4-10)-NH2) and III (Ac-[Nle4,Asp5,D-Phe7,Dap10]alpha-MSH(4-10)-NH2 all show very similar conformational properties (backbone and side-chain torsional angles), and all display high biological potencies. The modeling results for these compounds are supported by the NMR data. Peptide IV (Ac-c[Nle4,Asp5,D-Phe7,Dap10]alpha-MSH(4-10)-NH2) appears to have a markedly different conformation and has decreased biological potency.
Al-Obeidi
F
F
Department of Chemistry, University of Arizona, Tucson, USA.
O'Connor
S D
SD
Job
C
C
Hruby
V J
VJ
Pettitt
B M
BM
D000818:Animals; D003198:Computer Simulation; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D017433:Protein Structure, Secondary; D012867:Skin / Q000187:drug effects; D013329:Structure-Activity Relationship; D000521:alpha-MSH / Q000737:chemistry* / Q000494:pharmacology
D000521:alpha-MSH