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Interactions of lactone, carboxylate and self‐aggregated forms of camptothecin with human and bovine serum albumins
Author(s) -
Fleury Fabrice,
Kudelina Irina,
Nabiev Igor
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00204-4
Subject(s) - circular dichroism , chemistry , carboxylate , camptothecin , human serum albumin , stereochemistry , chromophore , binding site , bovine serum albumin , hydrophobic effect , biochemistry , organic chemistry
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.