title: Synthetic Fab fragments that bind the HIV-1 gp41 heptad repeat regions.
abstract: Recent work has demonstrated that antibody phage display libraries containing restricted diversity in the complementarity determining regions (CDRs) can be used to target a wide variety of antigens with high affinity and specificity. In the most extreme case, antibodies whose combining sites are comprised of only two residues - tyrosine and serine - have been identified against several protein antigens. [F.A. Fellouse, B. Li, D.M. Compaan, A.A. Peden, S.G. Hymowitz, S.S. Sidhu, J. Mol. Biol. 348 (2005) 1153-1162.] Here, we report the isolation and characterization of antigen-binding fragments (Fabs) from such "minimalist" diversity synthetic antibody libraries that bind the heptad repeat regions of human immunodeficiency virus type 1 (HIV-1) gp41. We show that these Fabs are highly specific for the HIV-1 epitope and comparable in affinity to a single chain variable fragment (scFv) derived from a natural antibody repertoire that targets the same region. Since the heptad repeat regions of HIV-1 gp41 are required for viral entry, these Fabs have potential for use in therapeutic, research, or diagnostic applications.
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Liu
authors.forename: Lauren K
authors.initials: LK
authors.lastname: Regula
authors.forename: Alex
authors.initials: A
authors.lastname: Stewart
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Lai
mesh_terms: D000595:Amino Acid Sequence; D000915:Antibody Affinity; D004797:Enzyme-Linked Immunosorbent Assay; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000276:immunology*; D008969:Molecular Sequence Data; D019151:Peptide Library; D017433:Protein Structure, Secondary; D012091:Repetitive Sequences, Nucleic Acid / Q000276:immunology; D012694:Serine / Q000737:chemistry; D014443:Tyrosine / Q000737:chemistry
chemical_list: D015700:HIV Envelope Protein gp41; D007140:Immunoglobulin Fab Fragments; D019151:Peptide Library; C514787:gp41 protein, Human immunodeficiency virus 1; D014443:Tyrosine; D012694:Serine