{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:17:48Z","timestamp":1789625868422,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,2,6]],"date-time":"2014-02-06T00:00:00Z","timestamp":1391644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Peptide Science"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:p>We have in the present study explored the anticancer activity against human Burkitt's lymphoma cells (Ramos) of a series of small linear and cyclic tetrapeptides containing a<jats:italic>\u03b2<\/jats:italic><jats:sup>2,2<\/jats:sup>\u2010amino acid with either two 2\u2010naphthyl\u2010methylene or two<jats:italic>para<\/jats:italic>\u2010CF<jats:sub>3<\/jats:sub>\u2010benzyl side chains, along with their interaction with the main plasma protein human serum albumin (HSA). The cyclic and more amphipathic tetrapeptides revealed a notably higher anticancer potency against Ramos cells [50% inhibitory concentration (IC<jats:sub>50<\/jats:sub>) 11\u201370\u2009\u03bcM] compared to the linear tetrapeptide counterparts (IC<jats:sub>50<\/jats:sub>18.7 to &gt;413\u2009\u03bcM). The most potent cyclic tetrapeptide c3 had a 16.5\u2010fold preference for Ramos cells compared to human red blood cells, whereas the cyclic tetrapeptide c1 both showed low hemolytic activity and displayed the overall highest (2.9\u2010fold) preference for Ramos cells (IC<jats:sub>50<\/jats:sub>23\u2009\u03bcM) compared to healthy human lung fibroblast cells (MRC\u20105). Investigating the interaction of selected tetrapeptides and recently reported hexapeptides with HSA revealed that the peptides bind to drug site II of HSA in the 22\u201328\u2009\u03bcM range, disregarding size and overall structure. NMR and<jats:italic>in silico<\/jats:italic>molecular docking experiments identified the lipophilic residues as responsible for the interaction, but<jats:italic>in vitro<\/jats:italic>studies showed that the anticancer potency of the peptides varied in the presence of HSA and that c3 remained the most potent peptide. Based on our findings, we call for implementing serum albumin binding in development of anticancer peptides, as it may have implications for future administration and systemic distribution of peptide\u2010based cancer drugs. Copyright \u00a9 2014 European Peptide Society and John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/psc.2615","type":"journal-article","created":{"date-parts":[[2014,2,6]],"date-time":"2014-02-06T05:37:25Z","timestamp":1391665045000},"page":"279-291","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Anticancer potency of small linear and cyclic tetrapeptides and pharmacokinetic investigations of peptide binding to human serum albumin"],"prefix":"10.1002","volume":"20","author":[{"given":"Annfrid","family":"Sivertsen","sequence":"first","affiliation":[{"name":"The Norwegian Structural Biology Centre, Department of Chemistry, Faculty of Science and Technology University of Troms\u00f8 NO\u20109037 Troms\u00f8 Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"T\u00f8rfoss","sequence":"additional","affiliation":[{"name":"Natural Products and Medicinal Chemistry Research 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