title: The antibody paradigm: present and future development as a scaffold for biopharmaceutical drugs.
abstract: Early studies of the humoral immune response revealed an apparent paradox: an infinite diversity of antibody specificities encoded within a finite genome. In consequence antibodies became a focus of interest for biochemists and geneticists. It resulted in the elucidation of the basic structural unit, the immunoglobulin (Ig) domain, comprised of ~ 100 amino acid residues that generate the characteristic "immunoglobulin (Ig) fold". The Ig fold has an anti-parallel ß-pleated sheet (barrel) structure that affords structural stability whilst the ß-bends allow for essentially infinite structural variation and functional diversity. This versatility is reflected in the Ig domain being the most widely utilised structural unit within the proteome. Human antibodies are comprised of multiple Ig domains and their structural diversity may be enhanced through the attachment of oligosaccharides. This review summarizes our current understanding of the immunoglobulin structure/function relationships and the application of protein and oligosaccharide engineering to further develop the Ig domain as a scaffold for the generation of new and novel antibody based therapeutics.
authors.affiliation: School of Immunity and Infection, The College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK. r.jefferis@bham.ac.uk
authors.forename: Roy
authors.initials: R
authors.lastname: Jefferis
mesh_terms: D000906:Antibodies / Q000737:chemistry* / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007107:Immune System / Q000502:physiology*; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D013678:Technology, Pharmaceutical / Q000639:trends*
chemical_list: D000906:Antibodies; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D008024:Ligands; D009844:Oligosaccharides