Deuterium NMR study of the MP-2269: albumin interaction — a step forward to the dynamics of non-covalent binding

✍ Scribed by Adzamli, K

• Book ID: 104390773
• Publisher: Springer
• Year: 2001
• Tongue: English
• Weight: 84 KB
• Volume: 12
• Category: Article
• ISSN: 0968-5243
• DOI: 10.1016/s1352-8661(01)00102-8

✦ Synopsis

MP-2269, the Gd(III) complex of 4-pentylbicyclo[2.2.2]octane-1-carboxyl-di-L-aspartyl-lysine-derived-DTPA, is a small Gdagent that binds non-covalently to serum albumin in vivo to assume the enhanced relaxivities associated with macromolecular agents, (due in part to increased rotational correlation time, ~R). To further explore the fundamental parameters that govern the dynamics of water proton relaxation enhancement by this prototypical albumin-binding agent, the rotational correlation time (~R) for the deuterated La(III) analog of MP-2269 has been independently measured in the presence and absence of 4% albumin using 2 H-NMR approaches. The diamagnetic La(III) analog of MP-2269 was deuterated at the a-position of the carbonyl groups. 2 H-NMR studies were conducted at 7.05T (46 MHz) and 310°K on a Bruker NMR spectrometer. Spectral deconvolution permitted calculation of transverse relaxation rates, 1/T 2 , from the NMR linewidths and subsequently, ~R. The results yielded a ~R of the albumin bound complex of 8 ns. This value is intermediate between those earlier estimated by 17 O-NMR ( 1 ns) and 1 H-NMRD ( 20-50 ns) and significantly shorter than that of albumin. The 2 H-NMR study results also indicate that the exchange between free and albumin-bound forms of the La(III) analog is slow (exchange lifetimes \1 ms). This slow exchange does not affect the water residence lifetimes (~M 140-280 ns).