A Surprising Message from Murines

  • Christian Schwabe
  • Erika E. Büllesbach


Rat relaxin had been known for about 18 years and had been thoroughly characterized mainly through by Sherwood et al.1–4 The relaxin used in those studies had been isolated by the method of Walsh et al in which homogenized ovaries were extracted with a mixture of trifluoroacetic acid (15%), formic acid (5%), sodium chloride (1%) and hydrochloric acid (1M).5,6 The conditions seemed rather rough but an active hormone was obtained which was used for all subsequent studies until very recently. Rat relaxin (Fig.13.1), always considered to be a relaxin of low potency, made a natural connection to our structure function studies, in particular the beneficial effect of replacement of histidine B10 in insulaxin for a glutamic acid. In the rat this position was occupied by glycine and based on a central dogma in protein chemistry, this was an unfavorable situation. Glycine is considered a helix-breaking residue and its presence in the major B chain helix right at the receptor interaction site seemed a clear indication that glycine B14 was compromising the bioactivity of rat relaxin. The opportunity was irresistible to test one’s ability to predict how certain features in a molecule would influence its bioactivity and subsequently to improve on a natural product. First rat relaxin was needed to establish a baseline and consequently a few milligrams were synthesized by the new method.7


Passive Immunization Protein Chemistry Human Relaxin Relaxin Receptor Crude Membrane Preparation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Sherwood OD. Purification and characterization of rat relaxin. Endocrinology 1979; 104: 886–892.PubMedCrossRefGoogle Scholar
  2. 2.
    Lao Guico-Lamm M, Sherwood OD. Monoclonal antibodies specific for rat relaxin: II passive immunization with monoclonal antibodies throughout the second half of pregnancy disrupts birth in intact rats. Endocrinology 1988; 123: 2479–2485.CrossRefGoogle Scholar
  3. 3.
    Kuenzi MJ, Sherwood OD. Monoclonal antibodies specific for rat relaxin: VII passive immunization with monoclonal antibodies throughout the second half of pregnancy prevents development of normal mammary nipple morphology and function in rats. Endocrinology 1992; 131: 1841–1847.PubMedCrossRefGoogle Scholar
  4. 4.
    Sherwood OD. Relaxin. In: Knobil E, Neill JD, eds. Physiology of Reproduction. Vol I. 2nd ed. New York: Raven Press, 1994861-IOmo.Google Scholar
  5. 5.
    Walsh JR, Niall HD. Use of an octadecylsilica purification method minimizes proteolysis during isolation of porcine and rat relaxin. Endocrinology 1980; 107: 1258–1260.PubMedCrossRefGoogle Scholar
  6. 6.
    John M, Borjesson BW, Walsh JR et al. Limited sequence homology between porcine and rat relaxins: Implication for physiological studies. Endocrinology 1981; 108: 726–729.PubMedCrossRefGoogle Scholar
  7. 7.
    Büllesbach EE, Schwabe C. The chemical synthesis of rat relaxin and the unexpectedly high potency of the synthetic hormone in the mouse. Eur J Biochem 1996; 241: 533–537.Google Scholar
  8. 8.
    DeGrado WF, Wasserman ZR, Lear JD. Protein design, a minimalist approach. Science 1989; 243: 622–628.CrossRefGoogle Scholar
  9. 9.
    Hecht MH, Richardson JS, Richardson DC et al. De Novo design, expression, and characterization of Felix: A four-helix bundle protein of native-like sequence. Science 1990; 249: 884–891.PubMedCrossRefGoogle Scholar
  10. 10.
    Mattos C, Ringe D. Locating and characterizing binding sites on proteins [Review]. Nature Biotechnology 1996; 14: 595–599.Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Christian Schwabe
    • 1
  • Erika E. Büllesbach
    • 1
  1. 1.Medical University of South CarolinaCharlestonUSA

Personalised recommendations