10.1002/chem.201002759
The research focuses on the conformational changes of spermine (SPM), a polyamine that plays a crucial role in various biological processes, when it interacts with adenosine triphosphate (ATP) and ATP–Mg2+ complexes. The study aims to understand the structural basis of the weak interactions between SPM and ATP, which are essential for cellular signal transduction and other biological functions. To achieve this, the researchers synthesized selectively 2H- and 13C-labeled SPMs and analyzed them using NMR spectroscopy to determine the spin–spin coupling constants for six conformationally relevant bonds. The experiments involved the preparation of labeled SPMs, measurement of stoichiometry and association constants in the SPM–ATP complex, and determination of spin–spin coupling constants under various conditions, including different pH levels and in the presence of ATP, ATP–Mg2+, and tripolyphosphate (TPP). The analyses provided insights into the binding affinity, stoichiometry, and conformational changes of SPM upon interaction with these complexes, revealing a preference of SPM for the adenyl group of ATP and its distinct interaction patterns compared to spermidine (SPD). These findings contribute to the understanding of the structural basis of polyamine biological functions.
10.1016/j.bmc.2009.11.013
The research describes the development of a novel anti-HIV polymeric prodrug: chitosan-O-isopropyl-50-O-d4T monophosphate conjugate. The study aims to improve the antiviral efficacy of nucleoside reverse transcriptase inhibitors (NRTIs) and reduce their side effects by constructing a nanosized NRTI monophosphate-polymer conjugate using d4T as a model NRTI. Key chemicals involved in the research include chitosan, a biodegradable and biocompatible polysaccharide used as the polymeric vehicle, and d4T (stavudine), an NRTI used in the treatment of HIV infection. The synthesis of the chitosan-d4T conjugate was achieved through the Atherton–Todd reaction under mild conditions, resulting in a water-soluble prodrug with a degree of substitution (DS) of 17.0%. Other chemicals used in the synthesis process include O-isopropyl-5-H-phosphonate of d4T, synthesized using phosphorus trichloride as a phosphorylation reagent, and various reagents such as triethylamine, tetrachloromethane, and sodium tripolyphosphate (TPP) for the preparation of nanoparticles. The study evaluated the anti-HIV activity and cytotoxicity of the conjugate in MT4 cells, prepared nanoparticles for enhanced delivery to viral reservoirs, and conducted in vitro drug release studies to assess the controlled release of d4T monophosphate derivatives.
Xi
