{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:43:00Z","timestamp":1787064180600,"version":"build-2736575974"},"reference-count":40,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry A European J"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Selective targeting of integrin \u03b1\n                    <jats:sub>V<\/jats:sub>\n                    \u03b2\n                    <jats:sub>6<\/jats:sub>\n                    is of high relevance for molecular imaging and therapeutic applications, yet ligands combining high affinity with structural and functional versatility remain limited. A structure\u2013activity relationship (SAR) study of the nonapeptide\n                    <jats:italic>cyclo<\/jats:italic>\n                    \u2010(\u2010Asp\u2010Leu\u2010Ala\u2010Phe\u2010\n                    <jats:sc>d<\/jats:sc>\n                    \u2010Pro\u2010NMeLys\u2010Phe\u2010Arg\u2010Gly\u2010) was performed through site\u2010specific substitution of phenylalanine residues by tryptophan and halogenated tryptophan derivatives, revealing a pronounced position\u2010dependent effect on integrin recognition. Substitution at position\n                    <jats:italic>i+3<\/jats:italic>\n                    relative to the RGD sequence with halotryptophans is identified as an affinity hotspot, enabling picomolar binding to \u03b1\n                    <jats:sub>V<\/jats:sub>\n                    \u03b2\n                    <jats:sub>6<\/jats:sub>\n                    . In contrast, modification at position\n                    <jats:italic>i+6<\/jats:italic>\n                    preserves high \u03b1\n                    <jats:sub>V<\/jats:sub>\n                    \u03b2\n                    <jats:sub>6<\/jats:sub>\n                    affinity while providing exceptional tolerance toward structural diversification and enabling late\u2010stage functionalization of unprotected peptides via palladium\u2010catalyzed cross\u2010coupling reactions. This establishes\n                    <jats:italic>i+6<\/jats:italic>\n                    modification as a versatile platform for chemoselective derivatization without compromising affinity. Halotryptophans serve both as pharmacophores and synthetic handles. Notably, an anthracenyl\u2010functionalized derivative combines sub\u2010nanomolar \u03b1\n                    <jats:sub>V<\/jats:sub>\n                    \u03b2\n                    <jats:sub>6<\/jats:sub>\n                    affinity with water solubility and intrinsic fluorescence, demonstrating that even bulky\n                    <jats:italic>\u03c0<\/jats:italic>\n                    \u2010systems can be accommodated at discrete positions without loss of potency. These integrin ligands are compatible with cellular applications and enable receptor\u2010specific detection by flow cytometry (FACS) as well as visualization by confocal fluorescence microscopy. This work defines a robust design for \u03b1\n                    <jats:sub>V<\/jats:sub>\n                    \u03b2\n                    <jats:sub>6<\/jats:sub>\n                    \u2010targeting functional probes for molecular imaging and fluorescence\u2010guided tumor detection.\n                  <\/jats:p>","DOI":"10.1002\/chem.71559","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:54:52Z","timestamp":1787061292000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Halogenated Tryptophans Improve Integrin \u03b1\n                    <sub>V<\/sub>\n                    \u03b2\n                    <sub>6<\/sub>\n                    Affinity of Cyclic RGD Peptides and Provide Handles for Late\u2010Stage Derivatization"],"prefix":"10.1002","author":[{"given":"Beate","family":"Nachtigall","sequence":"first","affiliation":[{"name":"Organic and Bioorganic Chemistry, Faculty 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Deutschland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0309-2655","authenticated-orcid":false,"given":"Norbert","family":"Sewald","sequence":"additional","affiliation":[{"name":"Organic and Bioorganic Chemistry, Faculty of Chemistry Bielefeld University, Universit\u00e4tsstra\u00dfe 25  Bielefeld 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