Graduate School of Science and Engineering , Kagoshima University , Kagoshima 890-0065 , Japan.
Tokai Quantum Beam Science Center , National Institutes for Quantum and Radiological Science and Technology , 2-4 Shirakata , Tokai, Ibaraki 319-1106 , Japan.
Bioconjug Chem. 2019 Mar 20;30(3):698-702. doi: 10.1021/acs.bioconjchem.8b00865. Epub 2019 Jan 16.
Artificially 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 residue (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, FcγRI, and FcγRIIIa), indicating that it is a suitable conjugate form that can be further developed into highly functional antibody therapeutics. CCAP was applied for the preparation of an antibody-drug conjugate and a bispecific antibody to demonstrate the usefulness of this method.
人工修饰的 IgG 分子在工业和临床应用中越来越受到重视。本研究开发了一种通过亲和肽进行化学偶联（CCAP）的方法，用于定点化学修饰，该方法使用与 IgG-Fc 高亲和力结合的肽。该方法能够在温和条件下一步反应快速修饰特定残基（Fc 上的 Lys248），在肽和 Fc 之间形成稳定的酰胺键。单价肽-IgG 缀合物不仅保持完全抗原结合，还与 Fc 受体（FcRn、FcγRI 和 FcγRIIIa）结合，表明它是一种合适的缀合形式，可以进一步开发成具有高度功能的抗体治疗药物。CCAP 被应用于制备抗体药物偶联物和双特异性抗体，以证明该方法的有用性。
