Abstract
In analyses of protein families that may serve as drug targets, membrane-associated G-protein-coupled receptors (GPCRs) dominate, followed by ion channels, transporters, and—to a lesser extent—membrane-bound enzymes. However, various challenges put such membrane proteins among key groups of underutilized opportunities for the application of therapeutic antibodies. Antibodies hold the promise of exquisite specificity, as they are able to target even specific conformations of a particular membrane protein, as well as adaptability through engineering into various antibody formats. However, the ease of raising and isolating specific, effective antibodies targeting membrane proteins depends on many factors. In particular, the generation of specific antibodies is easier when targeting larger, simpler, extracellular domains with greater uniqueness of amino acid sequence. The rareness of such ideal conditions is illustrated by the limited number of approved biologics for targeting GPCRs and other complex membrane proteins. Challenges in developing antibodies to complex membrane proteins such as GPCRs, ion channels, transporters, and membrane-bound enzymes can be addressed by the design of the antigen, antibody-generation strategies, lead optimization technologies, and antibody modalities. A better understanding of the membrane proteins being targeted would facilitate mechanism-based drug discovery. This review describes the advantages and challenges of targeting complex membrane proteins with antibodies and discusses the preparation of membrane protein antigens and antibody generation, illustrated by select examples of success.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.