Diana Gazis

Fluorescent, photoaffinity, and biotinyl analogs of oxytocin

This study reports the solid phase synthesis and biological activities of two oxytocin analogs, [1-desamino, 4-lysine,7-(L-3,4,-dehydroproline)]oxytocin and [1-desamino, 4-threonine,7-(L-3,4-dehydroproline),8-lysine]oxytocin, and several fluorescent, photoaffinity, or biotinylated derivatives of these analogs and of oxytocin. The activities (in IU/mg) of the lysine-containing parent compounds, respectively, were as follows: uterus (without Mg++) 4.8 and 54; uterus (with Mg++) 19 and 440; milk ejection 65 and 414. The above analogs were coupled through the chemically reactive epsilon-amino group of lysine in position 4 or 8 or, in the case of oxytocin, through the N-terminal amino group of fluoresceine, photoaffinity, or biotinyl ligands. Fluoresceine coupled in position 1 of oxytocin gave an analog of low to moderate uterine (3.8 without Mg+ and 1.9 with Mg++) and milk ejection (7.9) activities. Analogs with biotin or fluoresceine coupled to lysine in position 4 had moderate uterine (11 and 23 without Mg++; 38 and 11 with Mg++) and milk ejection (33 and 13) activities. Analogs with fluoresceine, photoaffinity, or biotinyl labels coupled to lysine in position 8 retained good uterine (106, 62, and 147 without Mg++; 79, 78, and 509 with Mg++) and milk ejection (101, 181, and 247) activities and represent potentially useful experimental tools for studying hormone-receptor interactions and for receptor localization and isolation.

4-Proline and 4-hydroxyproline analogs of arginine vasopressin: Role of the proline substitution in the two β-turns of vasopressin

[4-L-Proline]arginine vasopressin, [4-D-proline]arginine vasopressin, [4-hydroxyproline]arginine vasopressin and [4-proline, 7-hydroxyproline] arginine vasopressin were synthesized and found to have antidiuretic activities of 91±4, 1.7±0.2, 1.0±0.1 and 4.4±1.0 units/mg, respectively. None of these analogs exhibited a significant level of rat pressor activity. The observed activities of these and other analogs with substitutions at position 4 and/or 7 are discussed on the basis of hypotheses and data bearing on the solution conformation of vasopressins.