Importance of hydrophobic residues in alpha-human atrial natriuretic peptide (alpha-hANP) for vasorelaxant activity.
To investigate the roles of the hydrophobic residues in the ANP molecule on biological activities, we synthesized a series of analogs containing various phenylalanine-homologs in position 8 or methionine-homologs in position 12. Among the analogs [pCl-Phe8]-alpha-hANP(7-28) was 4.8 times as potent as alpha-hANP(7-28) in cGMP accumulation and 3.5 times as potent in vasorelaxant activity. All the analogs showed nanomolar affinity to the receptor. In contrast, vasorelaxation and cGMP accumulation activity of the analogs ranged widely. These results suggest that these hydrophobic residues in the cyclic core are critical for vasorelaxant activity rather than for the "apparent receptor binding", and that these residues may possibly discriminate the "bioactive receptor" which is coupled to guanylate cyclase from the non-coupled receptor.
Minamitake
Y
Y
Suntory Institute for Biomedical Research, Osaka, Japan.
Kitajima
Y
Y
Furuya
M
M
Yoshida
M
M
Tanaka
S
S
D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D008715:Methionine / Q000737:chemistry; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism*; D010649:Phenylalanine / Q000737:chemistry; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility; D014664:Vasodilation
D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D010649:Phenylalanine; D009320:Atrial Natriuretic Factor; D008715:Methionine; D017461:Receptors, Atrial Natriuretic Factor