整合素 αvβ5 介导的细胞粘附中含 RGD 肽的构效关系,ACS Omega

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整合素 αvβ5 介导的细胞粘附中含 RGD 肽的构效关系
ACS Omega ( IF 3.7 ) Pub Date : 2023-01-24 , DOI: 10.1021/acsomega.2c06540
Yuji Yamada ₁ , Toru Onda ₁ , Yuri Wada ₁ , Keisuke Hamada ₁ , Yamato Kikkawa ₁ , Motoyoshi Nomizu ₁

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RGD 基序是与整合素结合的细胞粘附序列，整合素是细胞外基质蛋白的受体家族。我们之前报道过，整合素 αvβ5 介导的细胞粘附需要RGDX ₁ X ₂序列，其中 X ₁ X _{2是 VF 或 NY。}_{然而，整合素αvβ5结合RGDX 1} X _2的X₁ X ₂组合及其周围序列的重要性和应用含肽尚未得到全面阐明。因此，我们旨在鉴定具有增强的整合素 αvβ5 结合活性的含有 RGD 的肽。我们基于 RGDVF 和 RGDNY 肽合成了多种肽，以优化RGDX ₁ X ₂的N 端、C 端和 X ₁ X _2组合顺序。这些肽通过硫醇-马来酰亚胺反应固定在马来酰亚胺功能化的牛血清白蛋白涂层板上，并使用 HeLa 细胞和人真皮成纤维细胞评估细胞粘附。因此，CPPP-RGDTF 和 CPPP-RGDTFI 被鉴定为整合素 αvβ5 介导的细胞粘附的高活性肽。CPPP-RGDTF 和 CPPP-RGDTFI 有望作为细胞粘附分子用于开发培养基质和生物材料。此外，这些发现为 RGD 基序和整合素之间的相互作用提供了重要的新见解。

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Structure–Activity Relationships of RGD-Containing Peptides in Integrin αvβ5-Mediated Cell Adhesion

The RGD motif is a cell adhesion sequence that binds to integrins, a receptor family for extracellular matrix proteins. We previously reported that the RGDX₁X₂ sequence, where X₁X₂ is VF or NY, is required for integrin αvβ5-mediated cell adhesion. However, the importance and applications of the X₁X₂ combinations and their surrounding sequences of integrin αvβ5-binding RGDX₁X₂-containing peptides have not been comprehensively elucidated. Therefore, we aimed to identify an RGD-containing peptide with enhanced integrin αvβ5 binding activity. We synthesized various peptides based on the RGDVF and RGDNY peptides to optimize the N-terminal, C-terminal, and X₁X₂ combinations of the RGDX₁X₂ sequence. These peptides were immobilized on maleimide-functionalized bovine serum albumin-coated plates via a thiol-maleimide reaction, and cell adhesion was evaluated using HeLa cells and human dermal fibroblasts. Consequently, CPPP-RGDTF and CPPP-RGDTFI were identified as highly active peptides for integrin αvβ5-mediated cell adhesion. CPPP-RGDTF and CPPP-RGDTFI are expected to serve as cell adhesion molecules for developing culture substrates and biomaterials. Furthermore, these findings provide important novel insights into the interaction between the RGD motifs and integrins.

更新日期：2023-01-24

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