title: Chemical synthesis of a Zwitterhormon, insulaxin, and of a relaxin-like bombyxin derivative.
abstract: The structural motif of insulin and relaxin is frequently seen in molecules of divergent functions and origins. The insect developmental factor bombyxin, the relaxin-like factor from Leydig cells, and the insulin-like factor 4 (INSL4) all are made of two disulfide-linked chains and have one disulfide bond within the A-chain. The polyclonal antibody R6, which was raised against porcine relaxin, reacts with a wide variety of naturally occurring relaxins from primates, marine and terrestrial mammals, and elasmobranchs but does not recognize insulin. The antibody binds mainly to the arginines that occur in the N, N+4 positions in the B-chains of all relaxins which also constitute the receptor-binding site. The receptor-binding haptens were incorporated by total synthesis into human despentapeptide insulin and bombyxin II, a developmental factor from the silk moth Bombyx mori. In the process the insect factor became a perfect antigen for the anti-relaxin antibody, whereas the human insulin was transformed into a bona fide relaxin. The conversion was affected by changing four critical residues so that the insulin activity was retained to the extent of 10% of the original level. This, to the best of our knowledge, is the first designer protein to incorporate two unrelated biological functions in one primary sequence, and we are therefore proposing that, analogous to zwitterion, the generic name "Zwitterhormon" (German spelling) be used for this type of construct.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston 29425, USA.
authors.forename: E E
authors.initials: EE
authors.lastname: Büllesbach
authors.forename: B G
authors.initials: BG
authors.lastname: Steinetz
authors.forename: C
authors.initials: C
authors.lastname: Schwabe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001681:Biological Assay; D002462:Cell Membrane / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D007328:Insulin / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000378:metabolism; D007985:Leydig Cells / Q000378:metabolism; D008297:Male; D008322:Mammals; D051379:Mice; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000378:metabolism; D010052:Ovariectomy; D010053:Ovary / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D011323:Primates; D011631:Pubic Symphysis / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000378:metabolism*; D012065:Relaxin / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013552:Swine
chemical_list: D007328:Insulin; D009479:Neuropeptides; D010446:Peptide Fragments; C077536:bombyxin II; D004958:Estradiol; D012065:Relaxin; D011972:Receptor, Insulin