We have used nuclear magnetic resonance to characterize the binding site of two intercellular adhesion molecule-1 derived cyclic peptides, cIBC and cIBR, to the I-domain of leukocyte function-associated antigen-1. These peptides inhibit the leukocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction known to play a key role in autoimmune diseases and cancer metastasis. Perturbation of the chemical shifts and intensities of the nuclear magnetic resonance signals corresponding to a number of residues of the I-domain of leukocyte function-associated antigen-1 show that both peptides bind to the I-domain allosteric site, the binding site of I-domain allosteric inhibitors such as lovastatin, and therefore the peptides probably also act as allosteric inhibitors of leukocyte function-associated antigen-1. Molecular models of the interaction of these two cyclic peptides with leukocyte function-associated antigen-1 I-domain show that the binding mode of the three molecules are analogous: the hydrophobic residues of the peptides remain buried and occupy the same positions as the apolar groups of lovastatin, while the peptides regions containing the most polar residues are flexible and primarily exposed to the solvent. These results suggest an allosteric mechanism for the inhibitory effect on T-cell adhesion displayed by both peptides, which exhibit potential as therapeutic agents.

中文翻译：

---

T细胞粘附的ICAM-1肽抑制剂与LFA-1的变构位点结合。NMR表征。

我们已经使用核磁共振来表征两个细胞间粘附分子1衍生的环状肽cIBC和cIBR与白细胞功能相关抗原1的I结构域的结合位点。这些肽抑制与白细胞功能相关的抗原1 /细胞间粘附分子1相互作用，这些相互作用在自身免疫性疾病和癌症转移中起关键作用。与白细胞功能相关抗原1的I结构域残基相对应的核磁共振信号的化学位移和强度的扰动表明，两种肽均与I结构变构位点（I的结合位点）结合-结构域变构抑制剂，例如洛伐他汀，因此这些肽也可能作为白细胞功能相关抗原-1的变构抑制剂。这两个环状肽与白细胞功能相关的抗原-1 I结构域相互作用的分子模型表明，这三个分子的结合模式是相似的：肽的疏水残基仍被掩埋并占据与非极性基团相同的位置洛伐他汀具有类似的活性，而含有最多极性残基的肽区域具有柔韧性，并且主要暴露在溶剂中。这些结果提示了两种肽都表现出对T细胞粘附的抑制作用的变构机制，这两种肽具有潜在的治疗作用。肽的疏水残基仍被掩埋并占据与洛伐他汀非极性基团相同的位置，而含有最多极性残基的肽区域则具有柔韧性并主要暴露于溶剂中。这些结果表明了两种肽都表现出对T细胞粘附的抑制作用的变构机制，这两种肽具有潜在的治疗作用。肽的疏水残基仍被掩埋并占据与洛伐他汀非极性基团相同的位置，而含有最多极性残基的肽区域则具有柔韧性并主要暴露于溶剂中。这些结果表明了两种肽都表现出对T细胞粘附的抑制作用的变构机制，这两种肽具有潜在的治疗作用。