Relaxin is an ovarian peptide hormone that is responsible for those tissue modifications that result in birth canal widening just prior to parturition. Relaxin is produced in the corpus luteum of pregnancy or in the placenta and is a disulfide homolog of insulin that exhibits neither biological insulin activity nor crossreactivity to antibodies raised against insulin. Besides the involvement in parturition relaxin may play a role in fertility in that the implantation of an ovum into the endometrium appears to be a relaxin-mediated process and sperm motility appears to be enhanced in the presence of relaxin. It has also been reported that relaxin exhibits an insulin-sparing activity during pregnancy and thus may be a potential drug for the treatment of pregnancy diabetes. The studies proposed here are aimed at an understanding of the relationship of relaxin structure to its various functions. The plan is to chemically dissect and reconstitute various aspects of the relaxin surface and to measure the effect of such modifications on the structural integrity and the biological activity of the molecule. One of the immediate goals is to identify the receptor interaction site of relaxin and to modify this interaction site in such a way that a covalent link with the receptor may be established. Chemical recognition sites have been added to the relaxin molecule in places where they do not interfere with biological activity and these sites should now serve to isolate the covalently-linked relaxin receptor complex. Attempts will then be made to obtain partial sequence information concerning the relaxin receptor that would eventually aid in the construction of a nucleotide probe with which a relaxin receptor-coding sequence may be isolated from the appropriate gene library.
|Bullesbach, Erika E; Hass, Mathias A S; Jensen, Malene R et al. (2008) Solution structure of a conformationally restricted fully active derivative of the human relaxin-like factor. Biochemistry 47:13308-17|
|Bullesbach, E E; Schwabe, C (1993) Mouse relaxin: synthesis and biological activity of the first relaxin with an unusual crosslinking pattern. Biochem Biophys Res Commun 196:311-9|