Insertion of an electronegative sulfur atom in the side chain of position 5 of angiotensin II: changes in the tachyphylactic properties of the peptide

Insertion of an electronegative sulfur atom in the side chain of position 5 of angiotensin II: changes in the tachyphylactic properties of the peptide

Autor Zalcberg, H. Google Scholar
Assimomytis, N. Google Scholar
Magafa, V Google Scholar
Manessi-Zoupa, E. Google Scholar
Cordopatis, P. Google Scholar
Shimuta, S. I. Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Univ Patras
Resumo Angiotensin II (All) analogs bearing n-Leu, Met or S-substituted groups for cysteine at position 5 were studied regarding their agonistic and tachyphylactic properties. It was shown that these analogs lowered the relative affinity towards the AT(1) receptor as determined by contractile responses, which could be due to the removal of the beta-branching residue at position 5. Insertion of a sulfur atom in a different position away from the attached backbone carbon atom presented no significant difference in EC50 values for these analogs. Interestingly, the S-bearing analogs at position 5 were full agonists but the tachyphylactic property was lost, in contrast to [n-Leu(5)]All, which still induced reduction of the contractile responses. Nevertheless after replacing the Asp with Sar in position 1 (Sar(1)) tachyphylaxis was again established. It is concluded that the insertion of Met or an S-substituted cysteine into the side chain at position 5 of All may promote interactions with its receptor due to the slight electronegative character of the sulfur atom and changes in the restricted conformational freedom of the lle(5) residue in the All molecule. This was overcome by Sar(1), probably through interactions due to its fully protonated N-terminal amino group and favoring the conformation responsible for the tachyphylaxis phenomenon.
Palavra-chave angiotensin II
AII analogs
guinea-pig ileum
tachyphylaxis
Idioma Inglês
Data de publicação 1999-06-01
Publicado em Journal of Peptide Research. Copenhagen: Munksgaard Int Publ Ltd, v. 53, n. 6, p. 678-681, 1999.
ISSN 1397-002X (Sherpa/Romeo, fator de impacto)
Publicador Munksgaard Int Publ Ltd
Extensão 678-681
Fonte http://dx.doi.org/10.1034/j.1399-3011.1999.00086.x
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000080973900012
Endereço permanente http://repositorio.unifesp.br/handle/11600/26092

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