{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:40:29Z","timestamp":1790016029864,"version":"4.0.1"},"reference-count":23,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2011,2,1]],"date-time":"2011-02-01T00:00:00Z","timestamp":1296518400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2011,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The influenza A virus polymerase complex, consisting of the subunits PB1, PB2, and PA, represents a promising target for the development of new antiviral drugs. We have previously demonstrated the feasibility of targeting the protein-protein interaction domain between PA and PB1 using peptides derived from the extreme N terminus of PB1 (amino acids [aa] 1 to 15), comprising the PA-binding domain of PB1. To increase the binding affinity of these peptides, we performed a systematic structure-affinity relationship analysis. Alanine and aspartic acid scans revealed that almost all amino acids in the core binding region (aa 5 to 11) are indispensable for PA binding. Using a library of immobilized peptides representing all possible single amino acid substitutions, we were able to identify amino acid positions outside the core PA-binding region (aa 1, 3, 12, 14, and 15) that are variable and can be replaced by affinity-enhancing residues. Surface plasmon resonance binding studies revealed that combination of several affinity-enhancing mutations led to an additive effect. Thus, the feasibility to enhance the PA-binding affinity presents an intriguing possibility to increase antiviral activity of the PB1-derived peptide and one step forward in the development of an antiviral drug against influenza A viruses.<\/jats:p>","DOI":"10.1128\/aac.01419-10","type":"journal-article","created":{"date-parts":[[2010,12,7]],"date-time":"2010-12-07T01:29:34Z","timestamp":1291685374000},"page":"696-702","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":55,"title":["Identification of High-Affinity PB1-Derived Peptides with Enhanced Affinity to the PA Protein of Influenza A Virus Polymerase"],"prefix":"10.1128","volume":"55","author":[{"given":"Kerstin","family":"Wunderlich","sequence":"first","affiliation":[{"name":"Department of Virology, University of Freiburg, 70104 Freiburg, Germany"},{"name":"Spemann Graduate School of Biology and Medicine, University of Freiburg, 70104 Freiburg, Germany"},{"name":"Faculty of Biology, University of Freiburg, 70104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mindaugas","family":"Juozapaitis","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology, LT-02241 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlene","family":"Ranadheera","sequence":"additional","affiliation":[{"name":"PiKe Pharma GmbH"},{"name":"Institute of Pharmaceutical Sciences, Swiss Federal Institute for Technology, CH-8093 Zu\u0308rich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Kessler","sequence":"additional","affiliation":[{"name":"PiKe Pharma GmbH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Virology, University of Freiburg, 70104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Eisel","sequence":"additional","affiliation":[{"name":"Department of Virology, University of Freiburg, 70104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Beutling","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology, Helmholtz Centre for Infection Research, D-38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Frank","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology, Helmholtz Centre for Infection Research, D-38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Schwemmle","sequence":"additional","affiliation":[{"name":"Department of Virology, University of Freiburg, 70104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.10.6716-6722.1996"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07745"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80066-5"},{"key":"e_1_3_2_5_2","first-page":"149","volume":"66","year":"1996","unstructured":"Frank, R., and H. 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