We have developed a straightforward and robust strategy for synthesizing a family of cyclic peptide scaffolds for the presentation of defined moieties in a wide range of orientations. Specifically we are exploring quinoxaline as the moiety, as a potential nucleic acid binding motif. The method requires the use of four degrees of orthogonality, which in turn allow the extension of the main chain, incorporation of the target side chains, on-resin cyclization, and the revelation of an amino group upon cleavage to increase solubility. We show that related approaches fail for a range of reasons, including the failure of cyclization. Following the optimization of the approach with a single cyclic peptide, we synthesized a family of all possible bis and tris quinoxaline adducts showing by ESI–MS that the desired full length cyclic product is produced in a majority of cases.

中文翻译：

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基于环肽高效合成支架的四正交策略。

我们已经开发出了一种简单而稳健的策略，用于合成环状肽支架家族，用于在各种方向上呈递定义的部分。具体而言，我们正在探索喹喔啉作为该部分，作为潜在的核酸结合基序。该方法需要使用四个正交度，依次允许主链延伸，目标侧链的掺入，树脂上的环化以及裂解时显示的氨基基团增加溶解度。我们显示了相关方法由于多种原因而失败，包括环化失败。在使用单一环肽对方法进行优化之后，