Fibrin specific peptides derived by phage display: characterization of peptides and conjugates for imaging.
Fibrin specific peptides derived by phage display: characterization of peptides and conjugates for imaging.
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DOI：
10.1021/bc200613e
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发表时间：
2012-03-21
影响因子：
4.7
通讯作者：
Caravan, Peter
中科院分区：
文献类型：
--
作者：
Kolodziej, Andrew F.;Nair, Shrikumar A.;Graham, Philip;McMurry, Thomas J.;Ladner, Robert C.;Wescott, Charles;Sexton, Daniel J.;Caravan, Peter
从噬菌体展示文库中选择与纤维蛋白结合但不与纤维蛋白原或血清白蛋白结合的肽作为血栓分子成像探针的靶向部分。通过共有序列 XArXCPY(G/D)LCArIX (Ar=芳香族，Tn6)、X2CXYYGTCLX (Tn7) 和 NHGCYNSYGVPYCDYS (Tn10) 鉴定了三类环肽（通过两个 Cys 之间的二硫键环化）。这些肽在约 2 个位点与纤维蛋白结合，Kd 分别为 4.1 μM、4.0 μM 和 8.7 μM，而与纤维蛋白原的结合至少弱 100 倍。这些肽还与纤维蛋白降解产物 DD(E) 结合，其亲和力与对纤维蛋白测量的亲和力相似。 Tn7 和 Tn10 肽结合到纤维蛋白上的同一位点，而 Tn6 肽结合到独特的位点。丙氨酸扫描发现 Tn6 和 Tn7 肽的 N 末端和 C 末端最耐受修饰。 N 末端与荧光素或二亚乙基三胺五乙酰钆 (III) (GdDTPA) 的肽缀合物被制备用于潜在的成像应用，并且这些缀合物保留了血浆中的纤维蛋白结合亲和力和特异性。 GdDTPA 衍生物的弛豫度和结合研究表明，N 端甘氨酰连接基对纤维蛋白亲和力影响不大，但会导致较低的纤维蛋白结合弛豫度。
Peptides that bind to fibrin but not to fibrinogen or serum albumin were selected from phage display libraries as targeting moieties for thrombus molecular imaging probes. Three classes of cyclic peptides (cyclized via disulfide bond between two Cys) were identified with consensus sequences XArXCPY(G/D)LCArIX (Ar=aromatic, Tn6), X2CXYYGTCLX (Tn7), and NHGCYNSYGVPYCDYS (Tn10). These peptides bound to fibrin at ~2 sites with Kd=4.1 μM, 4.0 μM, and 8.7 μM, respectively, whereas binding to fibrinogen was at least 100 – fold weaker. The peptides also bind to the fibrin degradation product DD(E) with similar affinity to that measured for fibrin. The Tn7 and Tn10 peptides bind to the same site on fibrin while the Tn6 peptides bind to a unique site. Alanine scanning identified the N- and C-terminal ends of the Tn6 and Tn7 peptides as most tolerant to modification. Peptide conjugates with either fluorescein or diethylenetriaminepentaaceto gadolinium(III) (GdDTPA) at the N-terminus were prepared for potential imaging applications and these retained fibrin binding affinity and specificity in plasma. Relaxivity and binding studies on the GdDTPA derivatives revealed that an N-terminal glycyl linker had modest effect on fibrin affinity but resulted in lower fibrin-bound relaxivity.
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影响因子：
37.8
作者：
Peter, K;Graeber, J;Bode, C
通讯作者：
Bode, C
影响因子：
37.8
作者：
Runge, MS;Harker, LA;Hanson, SR
通讯作者：
Hanson, SR
影响因子：
6.7
作者：
Vymazal, Josef;Spuentrup, Elmar;Parsons, Edward C., Jr.
通讯作者：
Parsons, Edward C., Jr.
影响因子：
8.3
作者：
Uppal R;Ay I;Dai G;Kim YR;Sorensen AG;Caravan P
通讯作者：
Caravan P
影响因子：
2.9
作者：
MOSKOWITZ, KA;BUDZYNSKI, AZ
通讯作者：
BUDZYNSKI, AZ