{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T05:16:11Z","timestamp":1766726171705,"version":"3.48.0"},"reference-count":42,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T00:00:00Z","timestamp":1766534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["2017\/09103-4"],"award-info":[{"award-number":["2017\/09103-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005942","name":"Butantan Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005942","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"crossref","award":["169527\/2023-9"],"award-info":[{"award-number":["169527\/2023-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002322","name":"Coordination for the Improvement of Higher Education Personnel","doi-asserted-by":"crossref","award":["015108\/2024-00"],"award-info":[{"award-number":["015108\/2024-00"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Peptidases constitute at least 2% of genes in living organisms and participate in nearly all physiological processes across life forms. Conversely, peptidase inhibitors are essential for regulating proteolytic activity and have been widely applied. Combining high-throughput sequencing of novel peptidase inhibitor sources with molecular modeling and drug design currently represents an efficient strategy for developing new molecules. Venomous spiders harbor a wide array of peptidase inhibitors in both their venom and digestive system. However, biochemical and transcriptomic investigations of non-venomous spiders (Uloboridae) remain recent and scarce. Here, transcriptomic and biochemical analyses of the Uloboridae spider Zosis geniculata\u2019s digestive midgut diverticula (MD) revealed that this species exhibited a digestive enzyme profile similar to that of other spiders. Furthermore, the MD transcriptome identified 19 peptidase inhibitors belonging to six inhibitor families. Serine peptidase inhibitors were the most abundant and diverse, while metallopeptidases represented the main proteolytic enzymes, suggesting that these inhibitors may have evolved to counteract prey-derived peptidases. Inhibitory assays using trypsin from potential insect prey confirmed this activity. The diversity and abundance of these molecules highlight Uloboridae spiders as promising novel sources of proteolytic inhibitors.<\/jats:p>","DOI":"10.3390\/ijms27010186","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T09:58:34Z","timestamp":1766570314000},"page":"186","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring Spiders Without Venom as New Sources of Peptidase Inhibitors"],"prefix":"10.3390","volume":"27","author":[{"given":"Jefferson O.","family":"Silva","sequence":"first","affiliation":[{"name":"Biotechnology Postgraduate Program, Institute of Biomedical Sciences, University of S\u00e3o Paulo, 2415 Professor Lineu Prestes Avenue, S\u00e3o Paulo 05508-000, Brazil"},{"name":"Biochemistry Laboratory, Butantan Institute, 1500 Vital Brazil Avenue, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Carolina O.","family":"Silva","sequence":"additional","affiliation":[{"name":"Biotechnology Postgraduate Program, Institute of Biomedical Sciences, University of S\u00e3o Paulo, 2415 Professor Lineu Prestes Avenue, S\u00e3o Paulo 05508-000, Brazil"},{"name":"Biochemistry Laboratory, Butantan Institute, 1500 Vital Brazil Avenue, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3180-0046","authenticated-orcid":false,"given":"Rodrigo","family":"Vallad\u00e3o","sequence":"additional","affiliation":[{"name":"Biochemistry Laboratory, Butantan Institute, 1500 Vital Brazil Avenue, S\u00e3o Paulo 05503-900, Brazil"},{"name":"Institute of Chemistry, Department of Biochemistry, University of S\u00e3o Paulo, 748 Professor Lineu Prestes Avenue, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar Bento","family":"Neto","sequence":"additional","affiliation":[{"name":"Biochemistry Laboratory, Butantan Institute, 1500 Vital Brazil Avenue, S\u00e3o Paulo 05503-900, Brazil"},{"name":"Institute of Chemistry, Department of Biochemistry, University of S\u00e3o Paulo, 748 Professor Lineu Prestes Avenue, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinicius Carius","family":"de Souza","sequence":"additional","affiliation":[{"name":"Special Laboratory of Applied Toxinology, Butantan Institute, 1500 Vital Brazil Avenue, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clelia","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, Department of Biochemistry, University of S\u00e3o Paulo, 748 Professor Lineu Prestes Avenue, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter Ribeiro","family":"Terra","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, Department of Biochemistry, University of S\u00e3o Paulo, 748 Professor Lineu Prestes Avenue, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9741-2110","authenticated-orcid":false,"given":"Adriana Rios","family":"Lopes","sequence":"additional","affiliation":[{"name":"Biotechnology Postgraduate Program, Institute of Biomedical Sciences, University of S\u00e3o Paulo, 2415 Professor Lineu Prestes Avenue, S\u00e3o Paulo 05508-000, Brazil"},{"name":"Biochemistry Laboratory, Butantan Institute, 1500 Vital Brazil Avenue, S\u00e3o Paulo 05503-900, Brazil"},{"name":"Institute of Chemistry, Department of Biochemistry, University of S\u00e3o Paulo, 748 Professor Lineu Prestes Avenue, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.biochi.2019.07.026","article-title":"Origins of peptidases","volume":"166","author":"Rawlings","year":"2019","journal-title":"Biochimie"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.2174\/1568026619666190619115243","article-title":"Protease inhibitors for the treatment of HIV\/AIDS: Recent advances and future challenges","volume":"19","author":"Voshavar","year":"2019","journal-title":"Curr. 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