Self-assembling DNA quadruplex conjugated to MRI contrast agents.
We report the preparation and magnetic resonance (MR) characterization of new MRI contrast agents based on gadolinium complexes conjugated to a self-assembling DNA quadruplex scaffold. As a single gadolinium-DOTA chelated DNA strand, the r(1) molar relaxivity is 6.4 mM(-1) s(-1) per Gd and increases to 11.7 mM(-1) s(-1) per Gd upon formation of a DNA quadruplex. Similar results were obtained when a gadolinium-DOTA dendrimer was conjugated to DNA, with the r(1) molar relaxivity increasing to 12.9 mM(-1) s(-1) per Gd upon the formation of DNA quadruplex, compared to that of 6.0 mM(-1) s(-1) for a single strand of gadolinium-DOTA dendrimer chelate. This yields an r(1) molar relaxivity of 154.8 and 46.8 mM(-1) s(-1) per DNA quadruplex based on DOTA dendrimer or monomer, respectively. Importantly, the DNA quadruplex scaffold is approximately 2.5 nm(3) in size, potentially enabling this type of contrast agent to be used for targeted delivery in vivo to detect specific cells or tissues, even behind intact blood vessels.
Cai
Jianfeng
J
Department of Chemistry, Yale University, 225 Prospect Street, New Haven, Connecticut 06511, USA.
Shapiro
Erik M
EM
Hamilton
Andrew D
AD
D001483:Base Sequence; D002614:Chelating Agents / Q000737:chemistry; D002942:Circular Dichroism; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry*; D050091:Dendrimers / Q000737:chemistry; D015195:Drug Design; D054856:G-Quadruplexes; D006571:Heterocyclic Compounds / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009942:Organometallic Compounds / Q000737:chemistry
D002614:Chelating Agents; D003287:Contrast Media; D050091:Dendrimers; D006571:Heterocyclic Compounds; D009838:Oligodeoxyribonucleotides; D009942:Organometallic Compounds; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate