Structural contribution of the A‐chain loop in relaxin
- 1 September 1995
- journal article
- Published by Wiley in International Journal of Peptide and Protein Research
- Vol. 46 (3-4) , 238-243
- https://doi.org/10.1111/j.1399-3011.1995.tb00595.x
Abstract
Site-directed sequential disulfide bond formation has been used to synthesize relaxin analogs with modifications in the A chain loop (AlO-A15). In the four different derivatives either the amino acid residues between the cysteines (A12-A14) were replaced or the intrachain disulfide bond (A10-A15) was eliminated. The substitution of the human relaxin 11 sequence (His-Val-Gly; A12-14) by the corresponding insulin sequence (Thr-Ser-Ile) or the hydrocarbon chain of ω-aminooctanoic acid (Aoc) caused significant loss of biological activity. Similar observations were made when the pair of cysteines (A10-A15) was replaced by either alanine or serine, whereby serine disturbs more than alanine. It is suggested that the structural features of the A chain loop not only make important contributions to the active conformation of relaxin but also that the structural requirements of insulin and relaxin are different.Keywords
This publication has 27 references indexed in Scilit:
- Insulin-like Compounds Related to the Amphioxus Insulin-like PeptideBiochemistry, 1994
- Total synthesis of human insulin by regioselective disulfide formation using the silyl chloride-sulfoxide methodJournal of the American Chemical Society, 1993
- Mouse Relaxin: Synthesis and Biological Activity of the First Relaxin with an Unusual Crosslinking PatternBiochemical and Biophysical Research Communications, 1993
- Steric requirements at position B12 for high biological activity in insulinBiochemistry, 1993
- Cardiac effects of relaxin in ratsThe Lancet, 1992
- Synthesis of bombyxin-IV, an insulin superfamily peptide from the silkworm,Bombyx mori, by stepwise and selective formation of three disulfide BridgesProtein Journal, 1992
- Possible involvement of the A20-A21 peptide bond in the expression of the biological activity of insulin. 1. [21-Desasparagine,20-cysteinamide-A]insulin and [21-desasparagine,20-cysteine isopropylamide-A]insulinBiochemistry, 1987
- Naturally occurring porcine relaxins and large-scale preparation of the B29 hormoneBiochemistry, 1985
- Eine verbesserte Methode der Kombination von Insulinketten zur Darstellung von InsulinanalogenHoppe-Seyler´s Zeitschrift Für Physiologische Chemie, 1981
- Human Proinsulin, VIII. Studies on the S-Tritylation of Reduced Proinsulin, Insulin A and B Chains and their DetritylationHoppe-Seyler´s Zeitschrift Für Physiologische Chemie, 1980