Mono-amine functionalized phthalocyanines: microwave-assisted solid-phase synthesis and bioconjugation strategies.
Phthalocyanines (Pcs) are excellent candidates for use as fluors for near-infrared (near-IR) fluorescent tagging of biomolecules for a wide variety of bioanalytical applications. Monofunctionalized Pcs, having two different types of peripheral substitutents, one for covalent conjugation of the Pc to biomolecules and others to improve the solubility of the macrocycle, are ideally suited for the desired applications. To date, difficulties faced during the purification of monofunctionalized Pcs limited their usage in various types of applications. Herein are reported a new synthetic method for rapid synthesis of the target Pcs and bioconjugation techniques for labeling of the oligonucleotides with the near-IR fluors. A novel synthetic route was developed utilizing a hydrophilic, poly(ethylene glycol) (PEG)-based support with an acid-labile Rink Amide linker. The Pcs were functionalized with an amine group for covalent conjugation purposes and were decorated with short PEG chains, serving as solubilizing groups. Microwave-assisted solid-phase synthetic method was successfully applied to obtain pure asymmetrically substituted monoamine functionalized Pcs in a short period of time. Three different bioconjugation techniques, reductive amination, amidation, and Huisgen cycloaddition, were employed for covalent conjugation of Pcs to oligonucleotides. The described microwave-assisted bioconjugation methods give an opportunity to synthesize and isolate the Pc-oligonucleotide conjugate in a few hours.
Erdem
S Sibel
SS
Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803, USA.
Nesterova
Irina V
IV
Soper
Steven A
SA
Hammer
Robert P
RP
D000577:Amides / Q000737:chemistry; D000588:Amines / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D054833:Isoindoles; D008872:Microwaves; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D012995:Solubility; D013997:Time Factors; D014867:Water / Q000737:chemistry
D000577:Amides; D000588:Amines; D007211:Indoles; D054833:Isoindoles; D009841:Oligonucleotides; D014867:Water; D011092:Polyethylene Glycols; C013647:phthalocyanine