Peptidyl Molecular Imaging Contrast Agents Using a New Solid-Phase Peptide Synthesis Approach

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• 作者：Byunghee Yoo ; Mark D. Pagel
• 刊名：Bioconjugate Chemistry
• 出版年：2007
• 出版时间：May 2007
• 年：2007
• 卷：18
• 期：3
• 页码：903 - 911
• 全文大小：311K
• 年卷期：v.18,no.3(May 2007)
• ISSN：1520-4812

文摘

A versatile method is disclosed for solid-phase peptide synthesis (SPPS) of molecular imaging contrast agents. ADO3A moiety was derivatized to introduce a CBZ-protected amino group and then coupled to a polymeric support.CBZ cleavage with Et₂AlCl/thioanisole was optimized for SPPS. Amino acids were then coupled to theaminoDOTA-loaded resin using conventional stepwise Fmoc SPPS to create a product with DOTA coupled tothe C-terminus of the peptide. In a second study, the DO3A moiety was coupled to a glycine-loaded polymericsupport, and amino acids were then coupled to the amino-DOTA-peptide-loaded resin using SPPS to incorporateDOTA within the peptide sequence. The peptide-(Tm³⁺-DOTA) amide showed a paramagnetic chemical exchangesaturation transfer (PARACEST) effect, which demonstrated the utility of this contrast agent for molecular imaging.These results demonstrate the advantages of exploiting SPPS methodologies through development of unique DOTAderivatives to create peptide-based molecular imaging contrast agents.