Polyamine Analogues Bind Human Serum Albumin

• Published in: Biomacromolecules Vol. 8; no. 10; pp. 3177 - 3183
• Main Authors: Beauchemin, R, N'soukpoé-Kossi, C. N, Thomas, T. J, Thomas, T, Carpentier, R, Tajmir-Riahi, H. A
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.10.2007
• Subjects: Applied sciences; Biological and medical sciences; Circular Dichroism; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; Humans; Hydrogen-Ion Concentration; In solution. Condensed state. Thin layers; Kinetics; Models, Chemical; Models, Molecular; Molecular biophysics; Natural polymers; Physico-chemical properties of biomolecules; Physicochemistry of polymers; Polyamines - chemistry; Polyamines - pharmacology; Protein Binding; Protein Denaturation; Protein Structure, Secondary; Proteins; Serum Albumin - chemistry; Software; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Spermine - analogs & derivatives; Spermine - pharmacology; Intermolecular interaction; Circular dichroism spectrum; Polyamine; Aliphatic compound; Animal protein; Serum albumin; Aqueous solution; Experimental study; Conformational transition
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm700697a

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 (μM 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 K 333 = 9.30 × 103 M-1, K BE-333 = 5.63 × 102 M-1, and K BE-3333 = 3.66 × 102 M-1. The protein secondary structure showed major alterations with a reduction of α-helix from 55% (free protein) to 43−50% and an increase of β-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.