Restriction of a peptide turn conformation and conformational analysis of guanidino group using arginine-proline fused amino acids: application to mini atrial natriuretic peptide on binding to the receptor.
Compounds (2S,4S)- and (2S,4R)-4-(2'-guanidinoethyl)proline have been synthesized as a conformationally restricted arginine. Their backbones fit the i + 1 position in a turn, and the side chains are restricted compared to that of arginine. These analogues were incorporated into mini atrial natriuretic polypeptide, which has an important turnlike conformation at Gly(6)-Arg(7)()-Met(8)-Asp(9). Structural analysis revealed that the size of the conformational space of Arg(7) on binding to the receptor was approximately one-third of the entire conformational space.
Sugase
Kenji
K
Suntory Institute for Bioorganic Research and Daiichi Suntory Biomedical Research Co., Ltd, Shimamoto, Mishima 618-8503, Japan.
Horikawa
Manabu
M
Sugiyama
Masako
M
Ishiguro
Masaji
M
D000818:Animals; D001120:Arginine / Q000737:chemistry*; D009320:Atrial Natriuretic Factor / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis; D006146:Guanidines / Q000737:chemistry*; D006162:Guanylate Cyclase / Q000187:drug effects* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010446:Peptide Fragments; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011392:Proline / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017461:Receptors, Atrial Natriuretic Factor / Q000187:drug effects* / Q000378:metabolism; D012996:Solutions; D013329:Structure-Activity Relationship
D006146:Guanidines; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D012996:Solutions; C482221:miniANP; C482220:miniANP, 4-(2'-guanidinoethyl)prolyl(7)-; D009320:Atrial Natriuretic Factor; D001120:Arginine; D011392:Proline; D000242:Cyclic AMP; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A