Biogenic and synthetic polyamines bind bovine serum albumin.
Biogenic polyamines are found to modulate protein synthesis at different levels, while polyamine analogues have shown major antitumor activity in multiple experimental models, including breast cancer. The aim of this study was to examine the interaction of bovine serum albumin (BSA) with biogenic polyamines, spermine and spermidine, and polyamine analogues 3,7,11,15-tetrazaheptadecane x 4 HCl (BE-333) and 3,7,11,15,19-pentazahenicosane x 5 HCl (BE-3333) in aqueous solution at physiological conditions. FTIR, UV-visible, CD, and fluorescence spectroscopic methods were used to determine the polyamine binding mode and the effects of polyamine complexation on protein stability and secondary structure. Structural analysis showed that polyamines bind BSA via both hydrophilic and hydrophobic interactions. Stronger polyamine-protein complexes formed with biogenic than synthetic polyamines with overall binding constants of K(spm) = 3.56 (+/-0.5) x 10(5) M(-1), K(spmd) = 1.77 (+/-0.4) x 10(5) M(-1), K(BE-333) = 1.11 (+/-0.3) x 10(4) M(-1) and K(BE-3333) = 3.90 (+/-0.7) x 10(4) M(-1) that correlate with their positively charged amino group contents. Major alterations of protein conformation were observed with reduction of alpha-helix from 63% (free protein) to 55-33% and increase of turn 12% (free protein) to 28-16% and random coil from 6% (free protein) to 24-17% in the polyamine-BSA complexes, indicating a partial protein unfolding. These data suggest that serum albumins might act as polyamine carrier proteins in delivering polyamine analogues to target tissues.
Dubeau
S
S
Département de Chimie-Biologie, Université du Québec à Trois-Rivières, C. P. 500, Trois-Rivières, Québec, G9A 5H7, Canada.
Bourassa
P
P
Thomas
T J
TJ
Tajmir-Riahi
H A
HA
D000818:Animals; D015317:Biogenic Polyamines / Q000138:chemical synthesis / Q000737:chemistry*; D002417:Cattle; D002942:Circular Dichroism; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D012995:Solubility; D012996:Solutions; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared
D015317:Biogenic Polyamines; D012996:Solutions; D012710:Serum Albumin, Bovine