Covalent Chemical Ligation Strategy for Mono- and Polyclonal Immunoglobulins at Their Nucleotide Binding Sites

Diana Lac, Chun Feng, Gaurav Bhardwaj, Huong Le, Jimmy Tran, Li Xing, Gabriel Fung, Ruiwu Liu, Holland Cheng, Kit Lam

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)159-169
Number of pages11
JournalBioconjugate Chemistry
Volume27
Issue number1
DOIs
StatePublished - Jan 20 2016

Fingerprint

Binding sites
Nucleotides
Antibodies
Ligation
Immunoglobulins
Binding Sites
Bispecific Antibodies
Immunoconjugates
Peptide Library
Immunoglobulin Fab Fragments
Lysine
Monoclonal Antibodies
Peptides
Ligands
Therapeutics
Pharmaceutical Preparations
Neoplasms

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Organic Chemistry
  • Pharmaceutical Science
  • Biomedical Engineering
  • Pharmacology

Cite this

Covalent Chemical Ligation Strategy for Mono- and Polyclonal Immunoglobulins at Their Nucleotide Binding Sites. / Lac, Diana; Feng, Chun; Bhardwaj, Gaurav; Le, Huong; Tran, Jimmy; Xing, Li; Fung, Gabriel; Liu, Ruiwu; Cheng, Holland; Lam, Kit.

In: Bioconjugate Chemistry, Vol. 27, No. 1, 20.01.2016, p. 159-169.

Research output: Contribution to journalArticle

Lac, Diana ; Feng, Chun ; Bhardwaj, Gaurav ; Le, Huong ; Tran, Jimmy ; Xing, Li ; Fung, Gabriel ; Liu, Ruiwu ; Cheng, Holland ; Lam, Kit. / Covalent Chemical Ligation Strategy for Mono- and Polyclonal Immunoglobulins at Their Nucleotide Binding Sites. In: Bioconjugate Chemistry. 2016 ; Vol. 27, No. 1. pp. 159-169.
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