title: Linking genotype to phenotype on beads: high throughput selection of peptides with biological function.
abstract: Although peptides are well recognised biological molecules in vivo, their selection from libraries is challenging because of relative low affinity whilst in linear conformation. We hypothesized that multiplexed peptides and DNA on the surface of beads would provide a platform for enhanced avidity and the selection of relevant peptides from a library (ORBIT bead display). Using human immunodeficiency virus (HIV-1) gp120 as a target, we identify peptides that inhibit HIV-1 replication in vitro through blocking of protein:protein interaction with the co-receptor CCR5. The bead display approach has many potential applications for probing biological systems and for drug lead development.
authors.affiliation: 1] MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, NIHR Biomedical Research Centre, University of Oxford, UK [2].
authors.forename: Li-Chieh
authors.initials: LC
authors.lastname: Huang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Pan
authors.forename: Hongbing
authors.initials: H
authors.lastname: Yang
authors.forename: Lai Kin Derek
authors.initials: LK
authors.lastname: Wan
authors.forename: Guillaume
authors.initials: G
authors.lastname: Stewart-Jones
authors.forename: Lucy
authors.initials: L
authors.lastname: Dorrell
authors.forename: Graham
authors.initials: G
authors.lastname: Ogg
mesh_terms: D019380:Anti-HIV Agents / Q000378:metabolism* / Q000494:pharmacology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D057166:High-Throughput Screening Assays; D006801:Humans; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D008863:Microspheres; D019151:Peptide Library; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D019713:Receptors, CCR5 / Q000378:metabolism; D015728:Receptors, HIV / Q000378:metabolism; D015203:Reproducibility of Results; D001613:beta 2-Microglobulin / Q000737:chemistry / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120; D019151:Peptide Library; D010455:Peptides; D019713:Receptors, CCR5; D015728:Receptors, HIV; D001613:beta 2-Microglobulin; C514793:gp120 protein, Human immunodeficiency virus 1