Solid phase synthetic methodology has been developed in our laboratory to incorporate an affinity label (a reactive functionality such as isothiocyanate or bromoacetamide) into peptides (Leelasvatanakij, L. and Aldrich, J. V. (2000) J. Peptide Res. 56, 80), and we have used this synthetic strategy to prepare affinity label derivatives of a variety of opioid peptides. To date side reactions have been detected only in two cases, both involving intramolecular cyclization. We have identified several peptide-based affinity labels for delta opioid receptors that exhibit wash-resistant inhibition of binding to these receptors and are valuable pharmacological tools to study opioid receptors. Even in cases where the peptide derivatives do not bind covalently to their target receptor, studying their binding has revealed subtle differences in receptor interactions with particular opioid peptide residues, especially Phe residues in the N-terminal "message" sequences. Solid phase synthetic methodology for the incorporation of other labels (e.g. biotin) into the C-terminus of peptides has also been developed in our laboratory (Kumar, V. and Aldrich, J. V. (2003) Org. Lett. 5, 613). These two synthetic approaches have been combined to prepare peptides containing multiple labels that can be used as tools to study peptide ligand-receptor interactions. These solid phase synthetic methodologies are versatile strategies that are applicable to the preparation of labeled peptides for a variety of targets in addition to opioid receptors.

中文翻译：

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标记肽衍生物的固相合成及应用：受体-阿片肽相互作用的探针。


我们的实验室已开发出固相合成方法，可将亲和标记（反应性官能团，如异硫氰酸酯或溴乙酰胺）整合到肽中（Leelasvatanakij, L. 和 Aldrich, JV (2000) J. Peptide Res. 56, 80），并且我们使用这种合成策略制备了多种阿片肽的亲和标记衍生物。迄今为止，仅在两种情况下检测到副反应，均涉及分子内环化。我们已经确定了几种基于肽的 δ 阿片受体亲和标记，这些标记对与这些受体的结合表现出耐洗涤抑制作用，是研究阿片受体的有价值的药理学工具。即使在肽衍生物不与其靶受体共价结合的情况下，研究它们的结合也揭示了受体与特定阿片肽残基（尤其是 N 端“信息”序列中的 Phe 残基）相互作用的细微差异。我们的实验室还开发了将其他标记（例如生物素）掺入肽 C 末端的固相合成方法（Kumar, V. 和 Aldrich, JV (2003) Org. Lett. 5, 613）。这两种合成方法已结合起来制备含有多个标记的肽，可用作研究肽配体-受体相互作用的工具。这些固相合成方法是通用策略，适用于制备除阿片受体外的各种靶标的标记肽。