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 ε{lunate}-amino group of lysine in position 4 or 8 or, in the case of oxytocin, through the N-terminal amino group to 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.