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Titolo:
TOWARDS MRI CONTRAST AGENTS OF IMPROVED EFFICACY - NMR RELAXOMETRIC INVESTIGATIONS OF THE BINDING INTERACTION TO HSA OF A NOVEL HEPTADENTATE MACROCYCLIC TRIPHOSPHONATE GD(III)-COMPLEX
Autore:
AIME S; BOTTA M; CRICH SG; GIOVENZANA GB; PAGLIARIN R; PICCININI M; SISTI M; TERRENO E;
Indirizzi:
UNIV TURIN,DIPARTIMENTO CHIM IFM,VIA P GIURIA 7 I-10125 TURIN ITALY UNIV MILAN,DIPARTIMENTO CHIM ORGAN & IND I-20133 MILAN ITALY
Titolo Testata:
JBIC. Journal of biological inorganic chemistry
fascicolo: 4, volume: 2, anno: 1997,
pagine: 470 - 479
SICI:
0949-8257(1997)2:4<470:TMCAOI>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTON RELAXATION ENHANCEMENT; HUMAN SERUM-ALBUMIN; MAGNETIC-RESONANCE; LANTHANIDE(III) COMPLEXES; ANIMAL BIODISTRIBUTION; WATER;
Keywords:
GD(III) COMPLEX; MRI CONTRAST AGENT; WATER EXCHANGE RATE; HUMAN SERUM ALBUMIN; RELAXOMETRY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
31
Recensione:
Indirizzi per estratti:
Citazione:
S. Aime et al., "TOWARDS MRI CONTRAST AGENTS OF IMPROVED EFFICACY - NMR RELAXOMETRIC INVESTIGATIONS OF THE BINDING INTERACTION TO HSA OF A NOVEL HEPTADENTATE MACROCYCLIC TRIPHOSPHONATE GD(III)-COMPLEX", JBIC. Journal of biological inorganic chemistry, 2(4), 1997, pp. 470-479

Abstract

A novel heptacoordinating ligand consisting of a thirteen-membered tetraazamacrocycle containing the pyridine ring and bearing three methylenephosphonate groups (PCTP-[13]) has been synthesized. Its Gd(III) complex displays a remarkably high longitudinal water proton relaxivity (7.7 mM(-1) s(-1) at 25 degrees C, 20 MHz and pH 7.5) which has been accounted for in terms of contributions arising from (1) one water molecule bound to the metal ion, (2) hydrogen-bonded water molecules in the second coordination sphere, or (3) water molecules diffusing near the paramagnetic chelate. Variable-temperature O-17-NMR transverse relaxation data indicate that the residence lifetime of the metal-bound water molecule is very short (8.0 ns at 25 degrees C) with respect to theGd(III) complexes currently considered as contrast agents for magnetic resonance imaging. Furthermore, GdPCTP-[13] interacts with human serum albumin (HSA), likely through electrostatic forces. By comparing water proton relaxivity data for the GdPCTP-[13]-HSA adduct, measured asa function of temperature and magnetic field strength, with those forthe analogous add;ct with GdDOTP (a twelve-membered tetraaza macrocyclic tetramethylene-phosphonate complex lacking a metal-bound water molecule), it has been possible to propose a general picture accounting for the main determinants of the relaxation enhancement observed when aparamagnetic Gd(III) complex is bound to HSA. Basically, the relaxation enhancement in these systems arises from (1) water molecules in thehydration shell of the macromolecule and protein exchangeable protonswhich lie close to the interaction site of the paramagnetic complex and (2) the metal bound water molecule(s). As far as the latter contribution is concerned, the interaction with the protein causes an elongation of the residence lifetime of the metal-bound water molecule, whichlimits, to some extent, the potential relaxivity enhancement expectedupon the binding of the paramagnetic complex to HSA.

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Documento generato il 29/09/20 alle ore 14:02:34