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Herein we investigate the role of Ctn[15\u201034] structure on serum survival. Using a set of analogs, we show that C\u2010terminal amidation, as well as the specific layout of the Ctn[15\u201034] sequence\u2014a helical N\u2010terminal domain followed by a hydrophobic domain\u2014is crucial for slow degradation, and any change in their arrangement results in significantly lower <jats:italic>t<\/jats:italic><jats:sub>1\/2<\/jats:sub>. Aside from the privileged primary structure, features such as self\u2010aggregation can be ruled out as causes for the long serum life. Instead, studies in other protease\u2010rich fluids suggest a key role for certain human serum components. Finally, we demonstrate that Ctn[15\u201034] is able to induce bacterial death even after 12\u2010hour pre\u2010incubation in serum, in agreement with the proteolytic data. Altogether, the results shed light on the uncommon stability of Ctn[15\u201034] in human serum and confirm its potential as an anti\u2010infective lead.<\/jats:p>","DOI":"10.1002\/psc.3195","type":"journal-article","created":{"date-parts":[[2019,7,18]],"date-time":"2019-07-18T06:48:09Z","timestamp":1563432489000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Structural determinants conferring unusual long life in human serum to rattlesnake\u2010derived antimicrobial peptide Ctn[15\u201034]"],"prefix":"10.1002","volume":"25","author":[{"given":"Clara","family":"P\u00e9rez\u2010Peinado","sequence":"first","affiliation":[{"name":"Department of Experimental and Health Science Universitat Pompeu Fabra, Barcelona Biomedical Research Park  Barcelona 08003 Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susana A.","family":"Dias","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa  Lisbon 1649\u2010028 Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diogo A.","family":"Mendon\u00e7a","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa  Lisbon 1649\u2010028 Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel A.R.B.","family":"Castanho","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa  Lisbon 1649\u2010028 Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana S.","family":"Veiga","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa  Lisbon 1649\u2010028 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