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-pentylbicyclo[2.2.2]octane-1-carboxyl-di-L-aspartyl-lysine-derived-DTPA, is a small Gd-agent 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, tau(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 (tau(R)) for the deuterated La(III) analog of MP-2269 has been independently measured in the presence and absence of 4% albumin using 2H-NMR approaches. The diamagnetic La(III) analog of MP-2269 was deuterated at the alpha-position of the carbonyl groups. 2H-NMR studies were conducted at 7.05T (46 MHz) and 310 degrees K on a Bruker NMR spectrometer. Spectral deconvolution permitted calculation of transverse relaxation rates, 1/T(2), from the NMR linewidths and subsequently, tau(R). The results yielded a tau(R) of the albumin bound complex of approximately 8 ns. This value is intermediate between those earlier estimated by 17O-NMR ( approximately 1 ns) and 1H-NMRD ( approximately 20-50 ns) and significantly shorter than that of albumin. The 2H-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 (tau(M) 140-280 ns).
Adzamli
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Imaging Division, Mallinckrodt Inc., 675 McDonnell Blvd., P.O. Box 5840, St. Louis, MO 63134, USA. kadzamli00@aol.com
Vander Elst
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Laurent
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Muller
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D003287:Contrast Media / Q000737:chemistry*; D003903:Deuterium; D005682:Gadolinium; D019786:Gadolinium DTPA / Q000031:analogs & derivatives / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000295:instrumentation / Q000379:methods; D012709:Serum Albumin / Q000737:chemistry*
D003287:Contrast Media; C112668:MP 2269; D012709:Serum Albumin; D003903:Deuterium; D005682:Gadolinium; D019786:Gadolinium DTPA