A new strategy for the preparation of peptide-targeted radiopharmaceuticals based on an fmoc-lysine-derived single amino acid chelate (SAAC). automated solid-phase synthesis, NMR characterization, and in vitro screening of fMLF(SAAC)G and fMLF[(SAAC-Re(CO)3)+]G.
A tridentate single amino acid chelate (SAAC) derived from N-alpha-Fmoc-l-lysine was incorporated within a short peptide sequence using an automated peptide synthesizer. Novel derivatives of the chemotactic peptide fMLF were prepared such that the SAAC and its Re complex were selectively placed between a terminal glycine amino acid and the targeting fMLF sequence. The products, which were synthesized in parallel, were characterized by mass spectrometry and multi-NMR spectroscopy. The latter technique demonstrated that the structures of the targeting portions of the peptides are the same in the SAAC and Re-SAAC derivatives. The affinities of the reported compounds for the formyl peptide receptor were subsequently determined using flow cytometry and were found to be comparable to that of the parent peptide. The results of this work demonstrate the feasibility and numerous benefits of using the SAAC system to prepare peptide-targeted Tc(I) and Re(I) radiopharmaceuticals.
Stephenson
Karin A
KA
Department of Chemistry and The Medical Physics and Applied Radiation Sciences Unit, McMaster University, Hamilton, ON, Canada L8S 4M1.
Zubieta
Jon
J
Banerjee
Sangeeta Ray
SR
Levadala
Murali K
MK
Taggart
Linda
L
Ryan
Lorna
L
McFarlane
Nicole
N
Boreham
Douglas R
DR
Maresca
Kevin P
KP
Babich
John W
JW
Valliant
John F
JF
D000465:Algorithms; D000596:Amino Acids / Q000737:chemistry*; D002614:Chelating Agents / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D056831:Coordination Complexes / Q000138:chemical synthesis*; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007962:Leukocytes / Q000187:drug effects; D008239:Lysine / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D018000:Receptors, Peptide / Q000187:drug effects; D012211:Rhenium / Q000737:chemistry*
D000596:Amino Acids; D002614:Chelating Agents; D056831:Coordination Complexes; D007202:Indicators and Reagents; D019275:Radiopharmaceuticals; D018000:Receptors, Peptide; C482339:tricarbonyl(N(alpha)-fluorenylmethoxycarbonyl-N(epsilon),N(epsilon)-bis(pyridin-2-ylmethyl)lysine)rhenium(I); D012211:Rhenium; D008239:Lysine