title: Rapid screening of peptide probes through in situ single-bead sequencing microarray.
abstract: 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.
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology of China , Beijing 100190, China.
authors.forename: Weizhi
authors.initials: W
authors.lastname: Wang
authors.forename: Zewen
authors.initials: Z
authors.lastname: Wei
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.forename: Huailei
authors.initials: H
authors.lastname: Ma
authors.forename: Zihua
authors.initials: Z
authors.lastname: Wang
authors.forename: Xiangli
authors.initials: X
authors.lastname: Bu
authors.forename: Menglin
authors.initials: M
authors.lastname: Li
authors.forename: Lingling
authors.initials: L
authors.lastname: Geng
authors.forename: Christopher
authors.initials: C
authors.lastname: Lausted
authors.forename: Leroy
authors.initials: L
authors.lastname: Hood
authors.forename: Qiaojun
authors.initials: Q
authors.lastname: Fang
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D046210:Microfluidic Analytical Techniques; D015394:Molecular Structure; D019151:Peptide Library; D010455:Peptides / Q000032:analysis*; D040081:Protein Array Analysis
chemical_list: D005456:Fluorescent Dyes; D019151:Peptide Library; D010455:Peptides