Synthesis of N-(2-chloro purin-6-yl) aza-18-crown-6 and its interaction with human serum albumin

Abstract

The synthesis of novel purine nucleosides-linked azacrown ethers in the C6 position, N-(2-chloro purin-6-yl) aza-18-crown-6 (NCPAC), was described. This new nucleoside analogue can be prepared from a series of N9-modified nucleosides and the method allows for new and easy modification of the nucleosides. The interaction between NCPAC and human serum albumin (HSA) was studied using molecular docking and fluorescence techniques. Thermodynamics revealed that the interaction was entropy driven with predominantly hydrophobic forces. From the observed Föster's-type fluorescence resonance energy transfer, the donor (Trp 214 in HSA) to acceptor (NCPAC) distance was calculated to be 3.6 nm. The conformational changes of HSA due to the interaction were investigated qualitatively from synchronous fluorescence spectra. Molecular docking studies were performed to obtain information on the possible residues involved in the interaction process.