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However, despite recent improvements in high\u2010throughput synthesis such as solid\u2010phase peptide synthesis in 384\u2010well plates, the size of synthetic peptide libraries is typically limited to a few thousand molecules. Herein we developed a strategy in which\n                    <jats:italic>m<\/jats:italic>\n                    short peptides with a thiol functional group are combinatorially paired with\n                    <jats:italic>n<\/jats:italic>\n                    short peptides of the same format by a disulfide bridge to generate\n                    <jats:italic>m<\/jats:italic>\n                    \u00a0\u00d7\u00a0\n                    <jats:italic>n<\/jats:italic>\n                    different peptide sequences. Using acoustic liquid transfer for rapid reagent transfer and formation of multiple peptide pairs per well in 1536\u2010well plates, we were able to screen over 800\u00a0000 different compounds that led to the identification of nanomolar inhibitors of the coagulation disorder protease thrombin. The concept of pairing synthetic peptide fragments might be applicable to other targets for identifying peptidic ligands below 1\u00a0kDa and thereby small enough to potentially deliver starting points for the development of membrane\u2010permeable drugs for oral application and\/or intracellular targeting.\n                  <\/jats:p>","DOI":"10.1002\/anie.3693802","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T03:55:10Z","timestamp":1788926110000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chemical Synthesis and Functional Screening of an 800\u00a0000\u2010Member Library Using a Peptide\u2010Pairing Strategy"],"prefix":"10.1002","author":[{"given":"Anne","family":"Zarda","sequence":"first","affiliation":[{"name":"Institute of Chemical Sciences and Engineering School of Basic Sciences \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL)  Lausanne 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