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

MP-2269, the Gd(III) complex of 4-pcntylbicyclo[2.2.2] octane-l-carboxyl-di-L-aspartyl-lysinc-derived-DTPA, is a small Gd-agent that binds non-covalently to scrum albumin in vivo to assume the enhanced relaxivities associated with macromolecular agents, (due in part to increased rotational correlation time, τR). 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 (τR) for the deuterated La(III) analog of MP-2269 has been independently measured in the presence and absence of 4% albumin using2H-NMR approaches. The diamagnetic La(III) analog of MP-2269 was deuterated at the α-position of the carbonyl groups.2H-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/T2, from the NMR linewidths and subsequently, τR. The results yielded a τR of the albumin bound complex of ∼ 8 ns. This value is intermediate between those earlier estimated by17O-NMR (∼ 1 ns) and1H-NMRD (∼ 20–50 ns) and significantly shorter than that of albumin. The2H-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 (τM 140-280 ns).