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While poly(ethylene glycol) (PEG)\u2010based PLs are the current standard, they are suspected to be responsible for rare adverse reactions, e. g. to LNP\u2010based Covid\u201019 vaccines. Therefore, PLs based on alternative stealth polymers are being intensively investigated for their use in LNPs. However, alternative PLs often lack comparability due to different synthesis protocols and are often not easily accessible. Herein we present a catalyst\u2010free, efficient and versatile coupling procedure for PL synthesis based on azide\u2010functionalized polymers and electron\u2010deficient acetylene dicarboxylate lipids. To highlight the versatility of this approach, we prepared PLs based on PEG and 4 alternative stealth polymers with quantitative coupling efficiencies. The linker structure showed appropriate pH stability and biocompatibility. All PLs enabled the preparation of well\u2010defined liposomes with excellent stability. Our facile and versatile approach yields comparable PLs with minimized linker size, making them promising candidates for future comparative studies, and biomedical applications.<\/jats:p>","DOI":"10.1002\/anie.202501262","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T02:52:21Z","timestamp":1742871141000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Electron\u2010Deficient Alkyne Lipids Enable Efficient Synthesis of Comparable Polymer Lipids via Copper\u2010Free Azide\u2010Alkyne Cycloaddition"],"prefix":"10.1002","volume":"64","author":[{"given":"Florian T.","family":"Kaps","sequence":"first","affiliation":[{"name":"Soft Matter Chemistry Department of Chemistry and Helsinki Institute of Sustainability Science Faculty of Science University of Helsinki  Helsinki 00014 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