Synthesis and AT2 receptor-binding properties of angiotensin II analogues
2004 (English)In: Journal of Peptide Research, ISSN 1397-002X, E-ISSN 1399-3011, Vol. 64, no 5, 194-201 p.Article in journal (Refereed) Published
The present study investigates the importance of the amino acid side chains in the octapeptide angiotensin II (Ang II) for binding to the AT2 receptor. A Gly scan was performed where each amino acid in Ang II was substituted one-by-one with glycine. The resulting set of peptides was tested for affinity to the AT2 receptor (porcine myometrial membranes). For a comparison, the peptides were also tested for affinity to the AT1 receptor (rat liver membranes). Only the substitution of Arg2 reduced affinity to the AT2 receptor considerably (92-fold when compared with Ang II). For the other Gly-substituted analogues the affinity to the AT2 receptor was only moderately affected. To further investigate the role of the Arg2 side chain for receptor binding, we synthesized some N-terminally modified Ang II analogues. According to these studies a positive charge in the N-terminal end of angiotensin III [Ang II (2–8)] is not required for high AT2 receptor affinity but seems to be more important in Ang II. With respect to the AT1 receptor, [Gly2]Ang II and [Gly8]Ang II lacked binding affinity (Ki > 10 μm). Replacement of the Val3 or Ile5 residues with Gly produced only a slight decrease in affinity. Interestingly, substitution of Tyr4 or His6, which are known to be very important for AT1 receptor binding, resulted in only 48 and 14 times reduction in affinity, respectively.
Place, publisher, year, edition, pages
2004. Vol. 64, no 5, 194-201 p.
angiotensin II, angiotensin III, AT1 binding, AT2 binding, Gly scan, peptide synthesis, structure–activity relationship
IdentifiersURN: urn:nbn:se:uu:diva-92324DOI: 10.1111/j.1399-3011.2004.00184.xOAI: oai:DiVA.org:uu-92324DiVA: diva2:165355