title: Selection of a potential diagnostic biomarker for HIV infection from a random library of non-biological synthetic peptoid oligomers.
abstract: Non-biological synthetic oligomers can serve as ligands for antibodies. We hypothesized that a random combinatorial library of synthetic poly-N-substituted glycine oligomers, or peptoids, could represent a random "shape library" in antigen space, and that some of these peptoids would be recognized by the antigen-binding pocket of disease-specific antibodies. We synthesized and screened a one bead one compound combinatorial library of peptoids, in which each bead displayed an 8-mer peptoid with ten possible different amines at each position (10(8) theoretical variants). By screening one million peptoid/beads we found 112 (approximately 1 in 10,000) that preferentially bound immunoglobulins from human sera known to be positive for anti-HIV antibodies. Reactive peptoids were then re-synthesized and rigorously evaluated in plate-based ELISAs. Four peptoids showed very good, and one showed excellent, properties for establishing a sero-diagnosis of HIV. These results demonstrate the feasibility of constructing sero-diagnostic assays for infectious diseases from libraries of random molecular shapes. In this study we sought a proof-of-principle that we could identify a potential diagnostic antibody ligand biomarker for an infectious disease in a random combinatorial library of 100 million peptoids. We believe that this is the first evidence that it is possible to develop sero-diagnostic assays - for any infectious disease - based on screening random libraries of non-biological molecular shapes.
authors.affiliation: Center for Vaccine Research, University of Pittsburgh, 3501 Fifth Ave, Pittsburgh, PA, 15261, United States.
authors.forename: Tricia L
authors.initials: TL
authors.lastname: Gearhart
authors.affiliation: Center for Vaccine Research, University of Pittsburgh, 3501 Fifth Ave, Pittsburgh, PA, 15261, United States.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Montelaro
authors.affiliation: Drug Discovery Institute, University of Pittsburgh, 3501 Fifth Ave, Pittsburgh, PA 15261, United States.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Schurdak
authors.affiliation: Center for AIDS Research, University of California, 1001 Potrero Ave, SFGH 80, San Francisco, CA 94110, United States.
authors.forename: Chris D
authors.initials: CD
authors.lastname: Pilcher
authors.affiliation: Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA, United States.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Rinaldo
authors.affiliation: The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, United States.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kodadek
authors.affiliation: Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA, United States.
authors.forename: Yongseok
authors.initials: Y
authors.lastname: Park
authors.affiliation: Peptide Synthesis Facility, University of Pittsburgh, 300 Technology Drive, Pittsburgh, PA 15219, United States.
authors.forename: Kazi
authors.initials: K
authors.lastname: Islam
authors.affiliation: Peptide Synthesis Facility, University of Pittsburgh, 300 Technology Drive, Pittsburgh, PA 15219, United States.
authors.forename: Raymond
authors.initials: R
authors.lastname: Yurko
authors.affiliation: Center for Vaccine Research, University of Pittsburgh, 3501 Fifth Ave, Pittsburgh, PA, 15261, United States; Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA, United States.
authors.forename: Ernesto T A
authors.initials: ET
authors.lastname: Marques
authors.affiliation: Center for Vaccine Research, University of Pittsburgh, 3501 Fifth Ave, Pittsburgh, PA, 15261, United States; Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA, United States. Electronic address: donburke@pitt.edu.
authors.forename: Donald S
authors.initials: DS
authors.lastname: Burke
mesh_terms: D015415:Biomarkers / Q000097:blood; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D015483:HIV Antibodies / Q000097:blood* / Q000276:immunology; D015658:HIV Infections / Q000175:diagnosis* / Q000276:immunology; D006801:Humans; D008024:Ligands; D019151:Peptide Library; D034444:Peptoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology*
chemical_list: D015415:Biomarkers; D015483:HIV Antibodies; D008024:Ligands; D019151:Peptide Library; D034444:Peptoids
keywords: Biomarker; Diagnostic; ELISA; HIV; Infectious disease; Peptoid