Yamada K M, Kennedy D W
J Cell Biochem. 1985;28(2):99-104. doi: 10.1002/jcb.240280203.
Synthetic peptides derived from the cell-binding domain of fibronectin have previously been found to inhibit fibronectin-mediated adhesion in vitro competitively and reversibly, as well as inhibiting cell migratory events in vivo. The amino acid sequence specificity required for this inhibitory activity has been examined further using variations of the originally identified active peptide sequences. The most active small peptide was found to be the pentapeptide Gly-Arg-Gly-Asp-Ser. Although the tetrapeptide Arg-Gly-Asp-Ser was found to retain substantial activity, it was approximately threefold less active. An "inverted" peptide sequence with these same four amino acids arranged in the mirror symmetrical sequence Ser-Asp-Gly-Arg was found to be nearly as active as the forward sequence. However, the same inverted tetrapeptide sequence embedded in a synthetic decapeptide derived from a sequence of histocompatibility antigens has minimal activity, suggesting the importance of adjacent sequences in modifying the activity of such peptides. Neither substitution of amino acids of the same charge nor reversal of the positions of the two charged amino acids retains biological activity. Decreasing the spacing between the charged residues also causes a loss of activity. Our results suggest the hypothesis that this adhesive recognition signal consists of a specific arrangement of one acidic and one basic charged group and additional information provided by adjacent amino acids.
先前已发现，源自纤连蛋白细胞结合域的合成肽在体外能竞争性且可逆地抑制纤连蛋白介导的黏附，在体内也能抑制细胞迁移活动。利用最初鉴定出的活性肽序列的变体，进一步研究了这种抑制活性所需的氨基酸序列特异性。发现活性最强的小肽是五肽甘氨酸 - 精氨酸 - 甘氨酸 - 天冬氨酸 - 丝氨酸。虽然发现四肽精氨酸 - 甘氨酸 - 天冬氨酸 - 丝氨酸仍保留相当的活性，但其活性约低三倍。发现具有相同四个氨基酸且以镜像对称序列丝氨酸 - 天冬氨酸 - 甘氨酸 - 精氨酸排列的“反向”肽序列，其活性几乎与正向序列相同。然而，嵌入源自组织相容性抗原序列的合成十肽中的相同反向四肽序列活性极小，这表明相邻序列在改变此类肽的活性方面很重要。相同电荷氨基酸的取代或两个带电荷氨基酸位置的颠倒均不能保留生物活性。减少带电荷残基之间的间距也会导致活性丧失。我们的结果提出了这样一个假说，即这种黏附识别信号由一个酸性和一个碱性带电基团的特定排列以及相邻氨基酸提供的额外信息组成。
