Polyamine analogues bind human serum albumin.
Polyamine analogues show antitumor activity in experimental models, and their ability to alter activity of cytotoxic chemotherapeutic agents in breast cancer is well documented. Association of polyamines with nucleic acids and protein is included in their mechanism of action. The aim of this study was to examine the interaction of human serum albumin (HSA) with several polyamine analogues, such as 1,11-diamino-4,8-diazaundecane (333), 3,7,11,15-tetrazaheptadecane.4HCl (BE-333), and 3,7,11,15,19-pentazahenicosane.5HCl (BE-3333), in aqueous solution at physiological conditions using a constant protein concentration and various polyamine contents (microM to mM). FTIR, UV-visible, and CD 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 nonspecifically (H-bonding) via polypeptide polar groups with binding constants of K333 = 9.30 x 10(3) M(-1), KBE-333 = 5.63 x 10(2) M(-1), and KBE-3333 = 3.66 x 10(2) M(-1). The protein secondary structure showed major alterations with a reduction of alpha-helix from 55% (free protein) to 43-50% and an increase of beta-sheet from 17% (free protein) to 29-36% in the 333, BE-333, and BE-3333 complexes, indicating partial protein unfolding upon polyamine interaction. HSA structure was less perturbed by polyamine analogues compared to those of the biogenic polyamines.
Beauchemin
R
R
Département de Chimie-Biologie, Université du Québec à Trois-Rivières, C P 500, Trois-Rivières (Québec), Canada.
N'soukpoé-Kossi
C N
CN
Thomas
T J
TJ
Thomas
T
T
Carpentier
R
R
Tajmir-Riahi
H A
HA
D002942:Circular Dichroism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D011073:Polyamines / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D012709:Serum Albumin / Q000737:chemistry*; D012984:Software; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology
C094172:1,15-bis(ethylamino)-4,8,12-triazapentadecane; D011073:Polyamines; D012709:Serum Albumin; C059685:N(1),N(11)-diethylnorspermine; D013096:Spermine