Interactions of lactone, carboxylate and self‐aggregated forms of camptothecin with human and bovine serum albumins

FEBS Letters

Kudelina, Irina²  Fleury, Fabrice¹  Nabiev, Igor¹ 

[1] Laboratoire de Spectroscopie Biomoléculaire, UFR de Pharmacie, Université de Reims, 51 rue Cognacq Jay, 51096 Reims Cedex, France;Optical Spectroscopy Division, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117871 Moscow, Russian Federation

关键词: Topoisomerase inhibitor;    Circular dichroism;    Camptothecin;    Human serum albumin;    topo I;    DNA topoisomerase I;    20(S)-CPT or CPT;    20(S)-camptothecin;    BSA;    bovine serum albumin;    CD;    circular dichroism;    PBS;    potassium buffered saline;   

DOI  :  10.1016/S0014-5793(97)00204-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Pronounced differences in the interactions of monomeric (lactone and carboxylate) and the J-type self-aggregated form of camptothecin (CPT), an inhibitor of DNA topoisomerase (topo) I, with human (HSA) and bovine (BSA) serum albumins were observed by using circular dichroism (CD) spectroscopy. HSA binding changes the geometry of the covalent structure of CPT due to hydrophobic contacts of the chromophore within the protein interior. The carbonyl group of the ring D of CPT (Fig. 1A) interacts with the positively charged amino acid residues of HSA. Interaction with HSA induces disaggregation of the J-type self-aggregates of CPT. On the other hand, neither heat-denatured HSA nor native BSA participated in binding of the lactone or carboxylate or self-aggregate forms of CPT. Analysis of HSA and BSA homology within the IIA and IIIA principle ligand-binding structural domains suggests that the binding site for the CPT chromophore is located in subdomain IIA. Hydrophobic contacts with Leu-203, Phe-211, and Ala-215 and electrostatic interactions with Lys-199 and/or Arg-222 of HSA may play a key role in formation of the drug-HSA complex.

【 授权许可】

Unknown