title: Covalent Chemical Ligation Strategy for Mono- and Polyclonal Immunoglobulins at Their Nucleotide Binding Sites.
abstract: Nonspecific ligation methods have been traditionally used to chemically modify immunoglobulins. Site-specific ligation of compounds (toxins or ligands) to antibodies has become increasingly important in the fields of therapeutic antibody-drug conjugates and bispecific antibodies. In this present study, we took advantage of the reported nucleotide-binding pocket (NBP) in the Fab arms of immunoglobulins by developing indole-based, 5-fluoro-2,4-dinitrobenzene-derivatized OBOC peptide libraries for the identification of affinity elements that can be used as site-specific derivatization agents against both mono- and polyclonal antibodies. Ligation can occur at any one of the few lysine residues located at the NBP. Immunoconjugates resulting from such affinity elements can be used as therapeutics against cancer or infectious agents.
authors.forename: Diana
authors.initials: D
authors.lastname: Lac
authors.forename: Chun
authors.initials: C
authors.lastname: Feng
authors.forename: Gaurav
authors.initials: G
authors.lastname: Bhardwaj
authors.forename: Huong
authors.initials: H
authors.lastname: Le
authors.forename: Jimmy
authors.initials: J
authors.lastname: Tran
authors.affiliation: Department of Molecular & Cellular Biology, University of California, Davis , Davis, California 95616, United States.
authors.forename: Li
authors.initials: L
authors.lastname: Xing
authors.forename: Gabriel
authors.initials: G
authors.lastname: Fung
authors.forename: Ruiwu
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Molecular & Cellular Biology, University of California, Davis , Davis, California 95616, United States.
authors.forename: Holland
authors.initials: H
authors.lastname: Cheng
authors.forename: Kit S
authors.initials: KS
authors.lastname: Lam
mesh_terms: D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D001391:Azo Compounds / Q000737:chemistry; D001665:Binding Sites; D001710:Biotin / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry*; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000378:metabolism; D007136:Immunoglobulins / Q000737:chemistry* / Q000378:metabolism; D007211:Indoles / Q000737:chemistry; D009711:Nucleotides / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D000068878:Trastuzumab / Q000737:chemistry
chemical_list: D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D001391:Azo Compounds; D003432:Cross-Linking Reagents; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D007136:Immunoglobulins; D007211:Indoles; D009711:Nucleotides; D009842:Oligopeptides; D019151:Peptide Library; D010455:Peptides; C014612:indolebutyric acid; C001413:HABA; D001710:Biotin; D000068878:Trastuzumab; C495575:monomethyl auristatin E