Rapid screening of peptide probes through in situ single-bead sequencing microarray.
Rapid screening of peptide probes through in situ single-bead sequencing microarray.
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DOI：
10.1021/ac503454z
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发表时间：
2014-11
影响因子：
7.4
通讯作者：
Weizhi Wang;Zewen Wei;Di Zhang;Huailei Ma;Zihua Wang;Xiangli Bu;Menglin Li;Lingling Geng;C. Lausted;L. Hood;Qiaojun Fang;Hao Wang;Zhiyuan Hu
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文献类型：
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作者：
Weizhi Wang;Zewen Wei;Di Zhang;Huailei Ma;Zihua Wang;Xiangli Bu;Menglin Li;Lingling Geng;C. Lausted;L. Hood;Qiaojun Fang;Hao Wang;Zhiyuan Hu
肽配体作为体内成像和药物递送的靶向探针引起了生物医学界的极大兴趣。然而，大肽文库的高亲和力和特异性筛选仍然是一个繁琐的过程。在这里，我们报告了一个连续流动的微流控方法的一珠一化合物（OBOC）的组合肽库筛选。我们在4小时内用2 × 10（5）个肽珠筛选了一个文库，发现了140个靶向肿瘤标志物氨肽酶N（APN）的非经典肽。利用Clustal算法，我们鉴定了N端的保守序列Tyr-XX-Tyr。我们证明了新序列YVEYHLC肽在离体和体内模型中对APN具有纳摩尔亲和力和高特异性。我们设想，这种用于肽筛选和鉴定的集成新型纳米技术的成功展示为快速发现用于疾病诊断和治疗的新的基于肽的试剂开辟了新的途径。
Peptide ligands as targeting probes for in vivo imaging and drug delivery have attracted great interest in the biomedical community. However, high affinity and specificity screening of large peptide libraries remains a tedious process. Here, we report a continuous-flow microfluidic method for one-bead-one-compound (OBOC) combinatorial peptide library screening. We screened a library with 2 × 10(5) peptide beads within 4 h and discovered 140 noncanonical peptide hits targeting the tumor marker, aminopeptidase N (APN). Using the Clustal algorithm, we identified the conserved sequence Tyr-XX-Tyr in the N terminal. We demonstrated that the novel sequence YVEYHLC peptides have both nanomolar affinity and high specificity for APN in ex vivo and in vivo models. We envision that the successful demonstration of this integrated novel nanotechnology for peptide screening and identification open a new avenue for rapid discovery of new peptide-based reagents for disease diagnostics and therapeutics.