Synthesis of Isoleucyl^5-Alanyl^7-Angiotensin Ⅱ

다국어 초록 (Multilingual Abstract)

The octapeptide isoleucyl -alanyl -angiotensin Ⅱ has been synthesized in order to study further the significance of structure at the C-terminal end of angiotesin Ⅱ for biological activity. This replacement of proline, in position 7 of angiotensin Ⅱ, by alanine, greatly reduced the pressor and oxytocic activites of the peptide. This marked loss of activity, by merely removing two methylene groups of the proline ring, may be caused by a changing of the confermation at the C-terminus of the peptide.
Addition of urea to an aqueous solution of angiotensin Ⅱ greatly reduces its myotrpohic action and also causes a marked reduction in degree of order showing bythe peptide as studied, by optical rotatory dispersion.
From this it follows that the conformation of the peptide is an important factor for the myotrophic activity.
Isoleucyl -angiotensin Ⅱ, the octapeptide L-aspartyl-L-arginyl-L-valyl-L_tyrosyl-L-isoleucyl-L-histidyl-L-prolyl-L-phenylalanine, exhibits marked specificty of structure at the C-terminus for pressor and myotrophic activities.
Removal of L-phenylalanine or only the aromatic ring of this amino acid destroys the biological activities of the peptide.
Conversion of the C-terminal carboxyl group to an amide group causes some reduction in biological activities.
The phenolic ring of tyrosine and the imidazole ring of histidine have also been reported to be essential for the biological activities of the peptide. A conformation recently suggested for angiotensin Ⅱ , based on the assumption it will form anα-helix to the greatest extent possible, will explain all physical and biological data presently known for this peptide. In this conformation the groups essential for biological activity are all arranged in close proximity and on the same side of the molecule.
Since rupture of the aliphatic ring of proline would change the stucture at the C-terminus of the peptide and would alter the relative position of these essential groups, we have replaced proline in angiotensin Ⅱ with alanine by the preparation of isoleucyl -ananyl angiotensin Ⅱ.