Stephenson Karin A, Zubieta Jon, Banerjee Sangeeta Ray, Levadala Murali K, Taggart Linda, Ryan Lorna, McFarlane Nicole, Boreham Douglas R, Maresca Kevin P, Babich John W, Valliant John F
Department of Chemistry and The Medical Physics and Applied Radiation Sciences Unit, McMaster University, Hamilton, ON, Canada L8S 4M1.
Bioconjug Chem. 2004 Jan-Feb;15(1):128-36. doi: 10.1021/bc034128s.
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.
使用自动肽合成仪将源自N-α-Fmoc-L-赖氨酸的三齿单氨基酸螯合物（SAAC）掺入短肽序列中。制备了趋化肽fMLF的新型衍生物，使得SAAC及其铼配合物选择性地置于末端甘氨酸氨基酸和靶向fMLF序列之间。平行合成的产物通过质谱和多维核磁共振光谱进行表征。后一种技术表明，SAAC和铼-SAAC衍生物中肽的靶向部分结构相同。随后使用流式细胞术测定了所报道化合物对甲酰肽受体的亲和力，发现其与亲本肽相当。这项工作的结果证明了使用SAAC系统制备肽靶向锝（I）和铼（I）放射性药物的可行性和诸多益处。
