Cyclic peptides are an attractive modality for the development of therapeutics and the identification of functional cyclic peptides that contribute to novel drug development. The peptide array is one of the optimization methods for peptide sequences and also useful to understand sequence–function relationship of peptides. Cell adherent cyclic NGR peptide which selectively binds to the aminopeptidase N (APN or CD13) is known as an attractive tumor marker. In this study, we designed and screened a library of different length and an amino acid substitution library to identify stronger cell adhesion peptides and to reveal that the factor of higher binding between CD13 and optimized cyclic peptides. Additionally, we designed and evaluated 192 peptide libraries using eight representative amino acids to reduce the size of the library. Through these optimization steps of cyclic peptides, we identified 23 peptides that showed significantly higher cell adhesion activity than cKCNGRC, which was previously reported as a cell adhesion cyclic peptide. Among them, cCRHNGRARC showed the highest activity, that is, 1.65 times higher activity than cKCNGRC. An analysis of sequence and functional data showed that the rules which show higher cell adhesion activity for the three basic cyclic peptides (cCX₁HNGRHX₂C, cCX₁HNGRAX₂C, and cCX₁ANGRHX₂C) are related with the position of His residues and cationic amino acids.

中文翻译：

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通过优化肽长度和氨基酸特征来提高细胞贴壁环状 NGR 肽的活性。

环肽是治疗药物开发和鉴定有助于新药物开发的功能性环肽的一种有吸引力的方式。肽阵列是肽序列的优化方法之一，也有助于理解肽的序列-功能关系。选择性结合氨肽酶 N（APN 或 CD13）的细胞粘附环状 NGR 肽被称为有吸引力的肿瘤标志物。在这项研究中，我们设计并筛选了一个不同长度的文库和一个氨基酸替代文库，以识别更强的细胞粘附肽，并揭示 CD13 与优化环肽之间具有更高结合的因素。此外，我们使用 8 个代表性氨基酸设计和评估了 192 个肽库，以减少库的大小。通过环肽的这些优化步骤，我们确定了 23 种肽，它们显示出比 cKCNGRC 显着更高的细胞粘附活性，cKCNGRC 以前被报道为细胞粘附环肽。其中cCRHNGRARC的活性最高，比cKCNGRC高1.65倍。对序列和功能数据的分析表明，三种基本环肽（cCX₁ HNGRHX ₂ C、cCX ₁ HNGRAX ₂ C 和 cCX ₁ ANGRHX ₂ C) 与 His 残基和阳离子氨基酸的位置有关。