Peptide inhibitors of fibronectin, laminin, and other adhesion molecules: Unique and shared features
Peptide inhibitors of fibronectin, laminin, and other adhesion molecules: Unique and shared features
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DOI：
10.1002/jcp.1041300105
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发表时间：
1987-01
影响因子：
5.6
通讯作者：
Kenneth M. Yamada;D. Kennedy
中科院分区：
文献类型：
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作者：
Kenneth M. Yamada;D. Kennedy
合成肽可以在体外和体内特异性抑制某些粘附糖蛋白的功能。我们比较了一组基于纤连蛋白序列的六种变体合成肽的相对活性，即它们抑制成纤维细胞与纤连蛋白、扩散因子/玻连蛋白、层粘连蛋白和天然胶原凝胶相互作用的能力。在这些粘附分子上扩散的 BHK（幼仓鼠肾）和鸡胚成纤维细胞对这组肽的抑制表现出独特的敏感性模式，这取决于粘附分子而不是细胞类型。对于纤连蛋白，Gly-Arg-Gly-Asp-Ser 的活性明显高于 Arg-Gly-Asp-Ser，而这两种肽在抑制细胞粘附至扩散因子方面的活性几乎没有差异。对于这两种蛋白质，反向肽序列 Ser-Asp-Gly-Arg 也具有中等活性，而包含转座、缺失或单个保守氨基酸取代的密切相关肽的活性则低得多。为了抑制与层粘连蛋白或天然 I 型胶原凝胶的相互作用，Gly-Arg-Gly-Asp-Ser 仅具有微弱活性，但反向肽 Ser-Asp-Gly-Arg 出人意料地继续对两种细胞类型中的两种附着蛋白表现出抑制活性。我们的结果表明，不同的粘附过程取决于细胞不同的肽识别事件。然而，附着蛋白之间可能存在一个对 Ser-Asp-Gly-Arg 中等敏感性的共同点。我们的研究还强调了当这些新型抑制剂用于表征生物过程时检查全套肽类似物的重要性。
Synthetic peptides can specifically inhibit the function of certain adhesive glycoproteins in vitro and in vivo. We have compared the relative activities of a set of six variant synthetic peptides based on the sequence of fibronectin in terms of their ability to inhibit the interactions of fibroblasts with fibronectin, spreading factor/vitronectin, laminin, and native collagen gels. BHK (baby hamster kidney) and chick embryo fibroblasts spreading on these adhesive molecules displayed distinctive patterns of sensitivity to inhibition by this panel of peptides, which depended on the adhesive molecule rather than the cell type. For fibronectin, Gly‐Arg‐Gly‐Asp‐Ser was considerably more active than Arg‐Gly‐Asp‐Ser, whereas these two peptides displayed little difference in activity in inhibiting cell adhesion to spreading factor. For both proteins, the inverted peptide sequence Ser‐Asp‐Gly‐Arg was also moderately active, whereas closely related peptides containing a transposition, a deletion, or a single, conserved amino acid substitution were much less active. For inhibiting interactions with laminin or native type I collagen gels, Gly‐Arg‐Gly‐Asp‐Ser was only weakly active, but the inverted peptide Ser‐Asp‐Gly‐Arg unexpectedly continued to display inhibitory activity for both attachment proteins in both cell types. Our results indicate that different adhesive processes depend on distinct peptide recognition events by a cell. However, there may be a possible common denominator among attachment proteins in a moderate sensitivity to Ser‐Asp‐Gly‐Arg. Our study also underscores the importance of examining a full set of peptide analogs when these novel inhibitors are used to characterize biological processes.