Biogenic and synthetic polyamines bind bovine serum albumin.
Biogenic and synthetic polyamines bind bovine serum albumin.
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DOI：
10.1021/bm100144v
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发表时间：
2010-06-14
影响因子：
6.2
通讯作者：
Tajmir-Riahi, H. A.
中科院分区：
文献类型：
--
作者：
Dubeau, S.;Bourassa, P.;Thomas, T. J.;Tajmir-Riahi, H. A.
生物多胺被发现在不同水平上调节蛋白质合成，而多胺类似物在多种实验模型中显示出主要的抗肿瘤活性，包括乳腺癌。本研究的目的是研究牛血清白蛋白（BSA）与生物多胺，精胺和亚精胺，以及多胺类似物3，7，11，15-tetrazaheptadecane. 4 HCl（BE-333）和3，7，11，15，19-pentazahenicosane. 5 HCl（BE-3333）在水溶液中的相互作用在生理条件下。采用红外光谱、紫外-可见光谱、圆二色光谱和荧光光谱等方法研究了多胺的结合方式以及多胺络合对蛋白质稳定性和二级结构的影响。结构分析表明，多胺结合BSA通过亲水和疏水相互作用。与生物多胺形成的多胺-蛋白质复合物比合成多胺更强，总结合常数Kspm = 3.56（±0.5）× 105 M-1，Kspmd = 1.77（±0.4）× 105 M-1，KBE-333 = 1.11（±0.3）× 104 M-1，KBE-3333 = 3.90（± 0.7）× 104 M-1，与其带正电荷的氨基含量有关。蛋白质构象发生了较大变化，α-螺旋从63%（游离蛋白）减少到55-33%，转角从12%（游离蛋白）增加到28-16%，无规卷曲从6%（游离蛋白）增加到24-17%，表明蛋白质部分解折叠。这些数据表明，血清白蛋白可能作为多胺载体蛋白在提供多胺类似物靶组织。
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.4HCl (BE-333) and 3,7,11,15,19-pentazahenicosane.5HCl (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 Kspm = 3.56 (±0.5) × 105 M-1, Kspmd = 1.77 (±0.4) × 105 M-1, KBE-333 = 1.11 (±0.3) × 104 M-1 and KBE-3333 = 3.90 (± 0.7) × 104 M-1 that correlate with their positively charged amino group contents. Major alterations of protein conformation were observed with reduction of α-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.
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影响因子：
6.2
作者：
Liang, Li;Tajmir-Riahi, H. A.;Subirade, Muriel
通讯作者：
Subirade, Muriel
影响因子：
3.3
作者：
Froehlich, E.;Mandeville, J. S.;Tajmir-Riahi, H. A.
通讯作者：
Tajmir-Riahi, H. A.
影响因子：
4.1
作者：
Huang, BX;Dass, C;Kim, HY
通讯作者：
Kim, HY
影响因子：
5.8
作者：
Arnold, K;Bordoli, L;Schwede, T
通讯作者：
Schwede, T
影响因子：
4.8
作者：
Dockal, M;Carter, DC;Rüker, F
通讯作者：
Rüker, F