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Their development, however, is synthetically demanding, as each receptor combination typically requires\n                    <jats:italic>de novo<\/jats:italic>\n                    preparation of large fusion peptides. We report a modular polyethylene glycol (PEG)\u2010based scaffold that enables orthogonal attachment of up to three functional components, including therapeutic peptides, half\u2010life\u2013extending units, and other labels, via sequential strain\u2010promoted azide\u2013alkyne cycloaddition (SPAAC) and copper\u2010catalysed azide\u2013alkyne cycloaddition (CuAAC). The scaffold is assembled on solid phase without intermediate purification, providing a readily accessible and versatile linker. Using glucagon\u2010like peptide\u20101 (GLP\u20101) and amylin receptor agonists as a proof\u2010of\u2010concept, dual\u2010agonist constructs with tuneable valency and functionality were rapidly generated. Lead conjugates displayed balanced, low\u2010picomolar potency at both receptors in cyclic adenosine monophosphate (cAMP) assays and showed selective receptor\u2010mediated internalisation in GLP\u20101 receptor\u2010expressing cells. This orthogonal click\u2010based platform enables rapid and modular multi\u2010agonist assembly, facilitating systematic exploration of receptor combinations, valency, and payload effects. Beyond incretin biology, it offers a general route to multifunctional peptide therapeutics and diagnostics.\n                  <\/jats:p>","DOI":"10.1002\/chem.71280","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T03:41:18Z","timestamp":1781840478000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Peptide Marriages: Modular Assembly of Multi\u2010Agonist Therapeutics"],"prefix":"10.1002","volume":"32","author":[{"given":"Kristina A.","family":"Kostadinova","sequence":"first","affiliation":[{"name":"Yusuf Hamied Department of Chemistry University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan L.","family":"Venne","sequence":"additional","affiliation":[{"name":"Yusuf Hamied Department of Chemistry University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0139-2360","authenticated-orcid":false,"given":"Sona","family":"Krajcovicova","sequence":"additional","affiliation":[{"name":"Yusuf Hamied Department of Chemistry University of Cambridge  Cambridge UK"},{"name":"Department of Organic Chemistry Faculty of Science Palacky University Olomouc  Olomouc Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Dodgson","sequence":"additional","affiliation":[{"name":"Biologics Engineering, Oncology R&amp;D AstraZeneca  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter F. 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