Alkyl chain dependent interactions of ligands with bovine serum albumin

The interactions of 2-(4′-N,N-dimethylamino)phenylimidazo[4,5-b]pyridine (DMAPIP-b), an inhibitor for aurora kinase and its long chain alkylated derivatives (1 and 2, Chart 1) with bovine serum albumin (BSA) are investigated. Both the effect of BSA on the spectral characteristics of the ligands and the effect of ligands on the spectral characteristics of BSA are studied. The fluorescence of all the three molecules increases substantially in the presence of protein. The alkylated molecules can sense BSA at lower concentration than DMAPIP-b. In the presence of BSA a 45 fold increase is observed in the fluorescent intensity of pyridine nitrogen alkylated molecule (1). The binding sites and the interactions of ligands depend on the presence and the position of alkyl chain. DMAPIP-b and molecule 1 quench the intrinsic fluorescence of BSA by energy transfer. On the other hand molecule 2 induces conformation change that leads to quenching of intrinsic fluorescence of BSA. Docking studies are also performed to support the experimental results.

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► A kinase inhibitor and its alkylated products interactions with BSA are studied.
► Weakly fluorescent molecules become strongly fluorescent upon binding with BSA.
► Kinase inhibitor and its pyridine nitrogen alkylated product bind at hydrophobic site.
► Imidazole nitrogen alkylated product binds at the hydrophilic site.
► Imidazole nitrogen alkylated product induces conformational change in BSA.