Combinatorial Peptide Libraries: Mining for Cell-Binding Peptides

被引:181
|
作者
Gray, Bethany Powell
Brown, Kathlynn C. [1 ]
机构
[1] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA
基金
美国国家卫生研究院;
关键词
PHAGE-DISPLAYED-PEPTIDE; TARGETED GENE-DELIVERY; TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR RECEPTOR; IN-VIVO SELECTION; BREAST-CANCER CELLS; VASCULAR ENDOTHELIAL-CELLS; HUMAN PROSTATE CARCINOMA; HIGH-AFFINITY PEPTIDES; NEURAL STEM-CELLS;
D O I
10.1021/cr400166n
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Methods of selecting cell-targeting ligands from peptide libraries and the use of these peptides were studied. While phage display methods have been the predominant library type used, other peptide library formats have also been used to isolate cell-targeting agents. Cell targeting peptides can have affinities comparable to those of clinically used antibodies and represent a new tool for directing targeting therapies and imaging agents. It is important to remember that the isolated ligands are rarely the optimal peptide sequence and should be considered lead compounds, yet by blending biology and chemistry, peptide leads can be optimized for affinity, specificity, activity, stability, solubility, and biodistribution. AMG-386 (trebananib), is in phase III clinical trials for treatment of a variety of cancer types. The peptide prevents binding of angiopoietin-1 and angiopoietin-2 to Tie2. The fat-targeting peptide CKGGRAKDC linked to the D-enantiomer of the proapoptotic (KLAKLAK)2 peptide entered phase I trial in early 2012 under the name Adipotide.
引用
收藏
页码:1020 / 1081
页数:62
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