6iqh
X-ray crystal structure of covalent-bonded complex of Fc and peptide
Structural highlights
FunctionIGG1_HUMAN Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins-secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (PubMed:22158414, PubMed:20176268). The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, after exposure to antigen and selection, allow affinity maturation for a particular antigen (PubMed:20176268, PubMed:17576170).[1] [2] [3] Publication Abstract from PubMedArtificially modified IgG molecules are increasingly utilized in industrial and clinical applications. In the present study, the method of chemical conjugation by affinity peptide (CCAP) for site-specific chemical modification has been developed by using a peptide that bound with high affinity to human IgG-Fc. This method enabled a rapid modification of a specific res-idue (Lys248 on Fc) in a one-step reaction under mild condition to form a stable amide bond between the peptide and Fc. The monovalent peptide-IgG conjugate not only maintained complete antigen binding but also bound to Fc receptors (FcRn, FcRgammaI, and FcRgammaIIIa), indicating that it is a suitable conjugate form that can be further developed into highly func-tional antibody therapeutics. CCAP was applied for the preparation of an antibody-drug conjugate and a bispecific anti-body to demonstrate the usefulness of this method. Site-specific chemical conjugation of antibodies by using affinity peptide for the development of therapeutic antibody format.,Kishimoto S, Nakashimada Y, Yokota R, Hatanaka T, Adachi M, Ito Y Bioconjug Chem. 2019 Jan 4. doi: 10.1021/acs.bioconjchem.8b00865. PMID:30606013[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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