Can the 1,5-disubstituted tetrazole ring modify the co-ordinating ability and biological activity of opiate-like peptides?
The copper(II) complexing ability and the biological activity of beta-casomorphin-7 tetrazole analogues have been investigated. Potentiometric and spectroscopic (UV-Vis, CD and EPR) studies have been used to establish the thermodynamic stability, speciation and structure of Cu(II) complexes with YP-psi(CN4)-FPGPI-NH2 (1), YPF-psi(CN4)-AGPI-NH2 (2) and YPFP-psi(CN4)-GPI-NH2 (3). Comparison of the binding ability of the tetrazole analogues reveals that the most effective ligand for copper(II) is YPF-psi(CN4)-AGPI-NH2. The effectiveness of this ligand comes from its particular conformation suited for the Cu(II) 2N co-ordination mode in the physiological pH region. The ability of casomorphin tetrazole analogues to activate rat mast cells to histamine release in vitro in the presence of copper(II) has been studied.
Lodyga-Chruscinska
E
E
Institute of General Food Chemistry, Technical University of Lódź, Poland. elalodyg@snack.p.lodz.pl
Brzezinska-Blaszczyk
E
E
Micera
G
G
Sanna
D
D
Kozlowski
H
H
Olczak
J
J
Zabrocki
J
J
Olejnik
A K
AK
D000818:Animals; D002942:Circular Dichroism; D003300:Copper / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D004723:Endorphins / Q000737:chemistry / Q000494:pharmacology*; D006632:Histamine / Q000096:biosynthesis; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D008956:Models, Chemical; D009294:Narcotics / Q000737:chemistry*; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D051381:Rats; D013053:Spectrophotometry; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D013816:Thermodynamics; D014466:Ultraviolet Rays
D004723:Endorphins; D008024:Ligands; D009294:Narcotics; D009842:Oligopeptides; D010455:Peptides; D013777:Tetrazoles; D003300:Copper; C021968:beta-casomorphins; D006632:Histamine