{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T15:31:25Z","timestamp":1787671885805,"version":"build-2736575974"},"reference-count":99,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"GREENVAN, LLC private investor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Monoclonal antibodies (mAbs) are widely used as therapeutic molecules for the treatment of serious diseases, primarily cancer. The market for mAbs is one of the fastest-growing segments of the biopharmaceuticals industry. Purification is a crucial stage in the production of mAbs. While staphylococcal protein A (SpA) affinity chromatography remains the gold standard in industrial mAb purification, its limitations\u2014low alkaline stability and insufficient binding capacity of SpA, as well as the need for harsh acidic elution conditions\u2014have driven extensive efforts for novel progressive affinity ligands. This review focuses on the development and performance of bacterial protein-based affinity resins for the purification of class G immunoglobulins (IgGs), including conventional proteins A and G, the promising protein L, and the more recently discovered protein M (from M. genitalium), each offering unique specificities for different antibody fragments and species. Hybrid ligands combining domains from multiple bacterial proteins are also discussed, along with next-generation synthetic alternatives such as affibodies, affimers, nanobodies, etc., as well as peptide-based or mixed-mode ligands. The key finding is that the reliable and time-tested resins like those based on protein A continue to dominate the market, although future trends also point toward smaller, more stable, and cost-effective synthetic ligands for specific applications.<\/jats:p>","DOI":"10.3390\/ijms27177618","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T15:01:07Z","timestamp":1787670067000},"page":"7618","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Overcoming the Limitations of Protein A: Evolution of Bacterial Protein-Based and Synthetic Affinity Ligands for High-Performance IgG Purification"],"prefix":"10.3390","volume":"27","author":[{"given":"Larisa N.","family":"Ikryannikova","sequence":"first","affiliation":[{"name":"I.M. Sechenov First Moscow State Medical University, Institute of Translational Medicine and Biotechnology, 8\/2 Trubetskaya Str., 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail N.","family":"Tereshin","sequence":"additional","affiliation":[{"name":"I.M. Sechenov First Moscow State Medical University, Institute of Translational Medicine and Biotechnology, 8\/2 Trubetskaya Str., 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena V.","family":"Baskova","sequence":"additional","affiliation":[{"name":"I.M. Sechenov First Moscow State Medical University, Institute of Translational Medicine and Biotechnology, 8\/2 Trubetskaya Str., 119991 Moscow, Russia"},{"name":"M.V. Lomonosov Institute of Fine Chemical Technologies, MIREA\u2014Russian Technological University, Vernadskogo Pr. 86, 119571 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina P.","family":"Telepenina","sequence":"additional","affiliation":[{"name":"I.M. Sechenov First Moscow State Medical University, Institute of Translational Medicine and Biotechnology, 8\/2 Trubetskaya Str., 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neonila V.","family":"Gorokhovets","sequence":"additional","affiliation":[{"name":"I.M. Sechenov First Moscow State Medical University, Institute of Translational Medicine and Biotechnology, 8\/2 Trubetskaya Str., 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel R.","family":"Bayzigitov","sequence":"additional","affiliation":[{"name":"R-Pharm Group Pharmaceutical Company, 119421 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenia A.","family":"Gurylina","sequence":"additional","affiliation":[{"name":"R-Pharm Group Pharmaceutical Company, 119421 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasiliy N.","family":"Stepanenko","sequence":"additional","affiliation":[{"name":"I.M. Sechenov First Moscow State Medical University, Institute of Translational Medicine and Biotechnology, 8\/2 Trubetskaya Str., 119991 Moscow, Russia"},{"name":"M.V. Lomonosov Institute of Fine Chemical Technologies, MIREA\u2014Russian Technological University, Vernadskogo Pr. 86, 119571 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7203-3449","authenticated-orcid":false,"given":"Tatiana D.","family":"Melikhova","sequence":"additional","affiliation":[{"name":"I.M. Sechenov First Moscow State Medical University, Institute of Translational Medicine and Biotechnology, 8\/2 Trubetskaya Str., 119991 Moscow, Russia"},{"name":"M.M. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str. 16\/10, 117437 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s43556-024-00210-1","article-title":"Monoclonal antibodies: From magic bullet to precision weapon","volume":"5","author":"Gohar","year":"2024","journal-title":"Mol. Biomed."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1007\/s11094-025-03444-7","article-title":"Analysis of the Use of Drugs Based on Monoclonal Antibodies in the Russian Federation","volume":"59","author":"Efremov","year":"2025","journal-title":"Pharm. Chem. 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