Conformationally constrained peptides from CD2 to modulate protein-protein interactions between CD2 and CD58.
Conformationally constrained peptides from CD2 to modulate protein-protein interactions between CD2 and CD58.
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DOI：
10.1021/jm200004e
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发表时间：
2011-08-11
影响因子：
7.3
通讯作者：
Satyanarayanajois, Seetharama D.
中科院分区：
文献类型：
--
作者：
Gokhale, Ameya;Weldeghiorghis, Thomas K.;Taneja, Veena;Satyanarayanajois, Seetharama D.
细胞黏附分子CD2及其配体CD58提供了细胞中参与免疫反应的蛋白质-蛋白质相互作用的很好例子。为了调节细胞间的黏附相互作用，根据CD2蛋白β-链区域的不连续表位设计了多肽。这两条链通过多肽键连接在一起。多肽中的β链通过插入β-折叠诱导(D)-Pro-Pro序列或二苯并呋喃(DBF)-转角模拟物与CD2蛋白的关键氨基酸序列结合而成核。用核磁共振和分子动力学模拟方法研究了多肽(5-10)的溶液结构。通过E-玫瑰花环试验和淋巴细胞上皮实验研究了这些多肽抑制细胞黏附相互作用的能力。在淋巴细胞-上皮细胞黏附实验中，多肽6和7抑制细胞黏附活性，IC50值分别为7 nM和11 nM。核磁共振和分子模拟结果表明，多肽6和7在溶液中具有β-发夹结构。
Cell adhesion molecule CD2 and its ligand CD58 provide good examples of protein-protein interactions in cells that participate in the immune response. To modulate the cell adhesion interaction, peptides were designed from the discontinuous epitopes of the β-strand region of CD2 protein. The two strands were linked by a peptide bond. β-strands in the peptides were nucleated by inserting a beta-sheet-inducing (D)-Pro-Pro sequence or a dibenzofuran (DBF)-turn mimetic with key amino acid sequences from CD2 protein that binds to CD58. The solution structures of the peptides (5–10) were studied by NMR and molecular dynamics simulations. The ability of these peptides to inhibit cell adhesion interaction was studied by E-rosetting and lymphocyte epithelial assays. Peptides 6 and 7 inhibit the cell adhesion activity with an IC50 value of 7 nM and 11 nM respectively, in lymphocyte-epithelial adhesion assay. NMR and molecular modeling results indicated that peptides 6 and 7 exhibited β-hairpin structure in solution.
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影响因子：
15
作者：
Andersen, Niels H.;Olsen, Katherine A.;Farazi, Shabnam R.
通讯作者：
Farazi, Shabnam R.
影响因子：
14.9
作者：
Davis IW;Leaver-Fay A;Chen VB;Block JN;Kapral GJ;Wang X;Murray LW;Arendall WB 3rd;Snoeyink J;Richardson JS;Richardson DC
通讯作者：
Richardson DC
影响因子：
5.6
作者：
Bahadur, RP;Chakrabarti, P;Janin, J
通讯作者：
Janin, J
DOI：
10.1107/s0907444909042073
发表时间：
2010-01
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Chen VB;Arendall WB 3rd;Headd JJ;Keedy DA;Immormino RM;Kapral GJ;Murray LW;Richardson JS;Richardson DC
通讯作者：
Richardson DC
影响因子：
2.9
作者：
Dyer, RB;Maness, SJ;Andersen, NH
通讯作者：
Andersen, NH