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However, limitations in their synthesis and efficiency of payload delivery restrict their clinical utility. Here we report a supramolecular assembly (SMA) ADC conjugation method, which allows site-specific, uniform drug loading, resulting in an enhanced pharmacokinetic profile and\n                  <jats:italic>in vivo<\/jats:italic>\n                  efficacy. This peptide conjugation strategy relies on spontaneous heterotetrameric coiled-coil formation between a pair of peptides appended on the C-terminus and a drug-loaded complementary pair in aqueous solution. Pairing this SMA conjugation with an antibody that targets the dual-endothlin-1\/VEGF signal peptide receptor (DEspR), a pancreatic ductal adenocarcinoma (PDAC) specific receptor, retains antibody binding and plasma stability. When the anti-DEspR monoclonal antibody is conjugated with monomethyl auristatin E (MMAE), the ensuing ADC internalizes following cell surface binding and induces selected cell death in multiple DEspR positive PDAC cell lines.\n                  <jats:italic>In vivo<\/jats:italic>\n                  , the ADC exhibits favorable pharmacokinetics, high tumor specificity, and improves overall survival in a rat orthotopic model of pancreatic peritoneal carcinomatosis, compared to conventional ADC conjugation. A heterotetrameric coiled-coil structure enables the efficient synthesis of a potent ADC, further documenting the versatility of supramolecular scaffolds as key orthogonal building block for site-specific conjugation in biopharmaceutical and biomaterial drug delivery systems.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>One Sentence Summary<\/jats:title>\n                  <jats:p>Combining site-specific conjugation of monomethyl auristatin E, via the use of biologically inspired heterotetrameric coiled-coils, with a tumor-selective antibody targeting the dual-endothlin-1\/VEGF signal peptide receptor affords a highly effective, ADC, which improves survival in a rat orthotopic model of pancreatic peritoneal carcinomatosis compared to standard cysteine-conjugated analogues with higher drug loading.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.08.05.743073","type":"posted-content","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T15:55:18Z","timestamp":1786031718000},"source":"Crossref","is-referenced-by-count":0,"title":["Supramolecular Site-Specific Antibody Drug Conjugates Outperform Cysteine-Conjugated Analogs in Pancreatic Peritoneal Carcinomatosis"],"prefix":"10.64898","author":[{"given":"Christopher M.","family":"Gromisch","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Yale University, New Haven, CT 06510"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6951-4032","authenticated-orcid":false,"given":"Alina","family":"Ringaci","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Boston University, Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aladin","family":"Hamoud","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Boston University, Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha M.","family":"Berry","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Boston University, Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Gromisch","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Yale University, New Haven, CT 06510"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2163-549X","authenticated-orcid":false,"given":"W. 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