Please use this identifier to cite or link to this item:
|Title:||Conformational studies of TOAC-labeled bradykinin analogues in model membranes|
Cilli, E. M.
Nakaie, C. R.
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
|Publisher:||Kluwer Academic Publ|
|Citation:||Letters in Peptide Science. Dordrecht: Kluwer Academic Publ, v. 9, n. 2-3, p. 83-89, 2002.|
|Abstract:||Spin-labeled analogues of bradykinin (BK) were synthesized containing the amino acid TOAC ( 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) either before Arg(1) (TOAC(0)-BK) or replacing Pro(3) (TOAC(3)-BK). Whereas the latter is inactive, the former retains about 70% of BK's activity in isolated rat uterus. A combined electron paramagnetic resonance (EPR)-circular dichroism ( CD) approach was used to examine the conformational properties of the peptides in the presence of membrane-mimetic systems ( negatively charged sodium dodecyl sulfate, SDS, and zwitterionic N-hexadecyl-N, N-dimethyl-3-ammonio-1-propanesulfonate, HPS). While the peptides bind to both monomeric and micellar SDS, no interaction occurs with HPS, evincing the contribution of electrostatic interactions. TOAC(3)-BK's EPR spectral lineshapes are broader than those of TOAC(0)-BK, indicating a more restricted degree of motion at position 3. Moreover, the motional freedom of both peptides decreased upon binding to SDS. BK and TOAC(0)-BK solution CD spectra indicate highly flexible conformations ( possibly an equilibrium between rapidly interconverting forms), while TOAC(3)-BK's spectra correspond to a more ordered structure. SDS binding induces drastic changes in BK and TOAC(0)-BK spectra, indicating stabilization of similar folds. the micelle interface promotes a higher degree of secondary structure by favoring intramolecular hydrogen bonds. in contrast, TOAC(3)-BK spectra remain essentially unchanged. These results are interpreted as due to TOAC's ring imposing a more constrained conformation. This rigidity is very likely responsible for the inability of TOAC(3)-BK to acquire the correct receptor-bound conformation, leading to loss of biological activity. On the other hand, the greater flexibility of TOAC(0)-BK and the similarity between its conformational behavior and that of the native hormone are probably related to their similar biological activity.|
|Appears in Collections:||Em verificação - Geral|
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.