PMID: 2120698Aug 1, 1990Paper

Site-specific attachment to recombinant antibodies via introduced surface cysteine residues

Protein Engineering
A LyonsJ R Adair

Abstract

Many diagnostic and therapeutic applications of monoclonal antibodies require the covalent linking of effector or reporter molecules to the immunoglobulin polypeptides. Existing methods generally involve the non-selective modification of amino acid side chains, producing one or more randomly distributed attachment sites. This results in heterogeneous labelling of the antibody molecules and often to a decrease in antigen-binding due to the modification of residues close to the antigen-binding site. We report a novel strategy for site-specifically labelling antibodies through surface cysteine residues. Examination of molecular structures was used to identify amino acids of the CH1 domain of the IgG heavy chain that were accessible to solvent but not to larger molecules. Site-directed mutagenesis was used to substitute cysteine residues at these positions in the heavy chain of a mouse/human chimaeric version of the tumour-binding monoclonal antibody, B72.3. Expression of the modified antibody genes in mammalian cells yielded correctly assembled proteins that had thiol groups in pre-determined positions and showed no loss of antigen-binding activity. One of the mutants was used to demonstrate the site-specific attachment of a radio...Continue Reading

Citations

Nov 10, 2009·Biochemistry·Thomas HoferChristoph Rader
Jun 10, 2008·The Cancer Journal·Paul J Carter, Peter D Senter
Mar 21, 2006·Biochemistry. Biokhimii︠a︡·N M GevondyanV S Gevondyan
Jul 22, 2008·Nature Biotechnology·Jagath R JunutulaWilliam Mallet
Jun 2, 2012·Expert Opinion on Biological Therapy·John R AdairKerry A Chester
Jan 23, 2016·Nature Chemistry·Vijay ChudasamaStephen Caddick
Mar 30, 2010·Nuclear Medicine and Biology·Jeff N TinianowJan Marik
Jan 22, 2015·The AAPS Journal·Jessica R McCombs, Shawn C Owen
Nov 19, 2013·Drug Discovery Today·Heidi L PerezRobert M Borzilleri
Dec 6, 2014·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·LeeRon Shefet-Carasso, Itai Benhar
Mar 1, 2017·Molecular Pharmaceutics·Nazzareno DimasiChangshou Gao
Jan 19, 2017·Marine Drugs·Yu-Jie WangBing-Hua Jiao
Jun 16, 2018·Angewandte Chemie·Coline CanovasVictor Goncalves
Dec 1, 1992·Immunological Reviews·J R Adair
Jul 6, 2000·The Journal of Biological Chemistry·J B StimmelF C Kull
Mar 24, 2016·Journal of Clinical Immunology·Dominik SchumacherJonas Helma
Jan 26, 2018·Protein Engineering, Design & Selection : PEDS·D SussmanD R Benjamin
Mar 7, 2021·Biomolecules·Thinzar M LwinMichael Bouvet
Jan 23, 2010·Bioconjugate Chemistry·Vladimir VoynovBernhardt L Trout
Sep 13, 2017·Chemical Reviews·Madduri Srinivasarao, Philip S Low

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.