Enzyme-Targeted Fluorescent Imaging Probes on a Multiple Antigenic Peptide Core

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• 作者：Amit K. Galande ; Scott A. Hilderbrand ; Ralph Weissleder ; Ching-Hsuan Tung
• 刊名：Journal of Medicinal Chemistry
• 出版年：2006
• 出版时间：July 27, 2006
• 年：2006
• 卷：49
• 期：15
• 页码：4715 - 4720
• 全文大小：322K
• 年卷期：v.49,no.15(July 27, 2006)
• ISSN：1520-4804

文摘

Peptide dendrimers have a variety of applications in biology such as the vehicles for drug and gene delivery,molecular inhibitors, protein mimics, and synthetic vaccines. The multiple antigenic peptide (MAP) systemis a well-known example of a discrete, dendrimeric scaffold. We explored a novel application of the MAP-based scaffold by designing molecular probes that fluoresce only after enzymatic treatment. The probes,which were synthesized on solid support, incorporate a cathepsin S dipeptide substrate (Leu-Arg), and apoly(ethylene glycol) (PEG) chain in their dendritic arms. The fluorescence emission of the near-infraredfluorochromes attached to the N-termini of the dendritic arms was quenched. Mechanistic studies revealedformation of H-type dye aggregates within the tetravalent MAP system. By varying the length of the PEGchain, three probes were synthesized, CyPEG-1, CyPEG-2, and CyPEG-3 with 4, 8, and 12 ethylene oxideunits, respectively. CyPEG-2 showed optimum aqueous solubility and quenching efficiency for imagingapplications. Upon proteolytic activation with cathepsin S (EC 3.4.22.27), CyPEG-2 showed greater than70-fold increase and more than 95% recovery in fluorescence emission.