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However, sortase\u00a0A (SrtA) suffers from low catalytic efficiency and mediates an equilibrium reaction. Therefore, ligations with large macromolecules may be challenging. Here, the synthesis of polymeric building blocks for sortase\u2010mediated ligation constituting peptide\u2010polymers with either the recognition sequence for sortase\u00a0A (LPX<jats:sub>1<\/jats:sub>TGX<jats:sub>2<\/jats:sub>) or its nucleophilic counterpart (G<jats:sub>x<\/jats:sub>) is demonstrated. The peptide\u2010polymers are synthesized by solid\u2010phase peptide synthesis followed by photo\u2010iniferter (PI) reversible addition\u2010fragmentation chain\u2010transfer (RAFT) polymerization of various monomers. The building blocks are subsequently utilized to investigate possibilities and limitations when using macromolecules in SML. In particular, diblock copolymers are obtained even when using the orthogonal building blocks in equimolar ratio by exploiting a technique to shift the reaction equilibrium. However, ligations of two polymers can not be achieved when the degree of polymerization exceeds 100. Subsequently, C\u2010terminal protein\u2010polymer conjugates are synthesized. Several polymers are utilized that can replace the omnipresent polyethylene glycol (PEG) in future therapeutics. The conjugation is exemplified with a nanobody that is known for efficient neutralization of SARS\u2010CoV\u20102. The study demonstrates a universal approach to polymer\u2010LPX<jats:sub>1<\/jats:sub>TGX<jats:sub>2<\/jats:sub> and G<jats:sub>x<\/jats:sub>\u2010polymer building blocks and gives insight into their application in SML.<\/jats:p>","DOI":"10.1002\/mabi.202400316","type":"journal-article","created":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T10:39:53Z","timestamp":1727951993000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Application of Sortase\u2010Mediated Ligation for the Synthesis of Block Copolymers and Protein\u2010Polymer Conjugates"],"prefix":"10.1002","volume":"25","author":[{"given":"Johannes","family":"Martin","sequence":"first","affiliation":[{"name":"Institute of Chemistry University of Potsdam  Karl\u2010Liebknecht\u2010Str. 24\u201325 14476 Potsdam\u2010Golm Germany"},{"name":"Fraunhofer Institute for Applied Polymer Research IAP  Geiselbergstr. 69 14476 Potsdam\u2010Golm 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