Effects of the substitution of photoreactive groups in positions 4 and 8 of vasopressin.
In an effort to synthesize potent vasopressin analogs containing photoreactive groups, we prepared, by solid phase synthesis, three analogs with proline or hydroxyproline substitutions in positions 4 and/or 7, lysine in positions 4 or 8, and beta-mercaptopropionic acid in position 1. From these three parent analogs, 1-desamino[4-proline,8-lysine]VP, 1-desamino[4-hydroxyproline,8-lysine]VP, and 1-desamino[4-lysine,7-hydroxyproline]AVP, we then prepared the corresponding azido compounds using the epsilon-amino group of lysine as the attachment point. These six analogs were then assayed for antidiuretic and pressor activities in rats. One of the resulting analogs, 1-desamino[4-lysine(N epsilon-4-azidobenzoyl),7-hydroxyproline)]AVP has the highest antidiuretic activity of any photoreactive compound reported to date.
Buku
A
A
Department of Physiology and Biophysics, Mount Sinai School of Medicine of CUNY, NY.
Yamin
N
N
Gazis
D
D
D000345:Affinity Labels; D000818:Animals; D001681:Biological Assay; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects; D006909:Hydroxyproline; D008239:Lysine; D010777:Photochemistry; D011392:Proline; D051381:Rats; D013329:Structure-Activity Relationship; D014667:Vasopressins / Q000138:chemical synthesis / Q000494:pharmacology
D000345:Affinity Labels; D014667:Vasopressins; D011392:Proline; D008239:Lysine; D006909:Hydroxyproline