{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T07:11:42Z","timestamp":1778829102727,"version":"3.51.4"},"reference-count":61,"publisher":"Wiley","issue":"36","license":[{"start":{"date-parts":[[2016,7,27]],"date-time":"2016-07-27T00:00:00Z","timestamp":1469577600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["HI1094\/5-1"],"award-info":[{"award-number":["HI1094\/5-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2016,8,26]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Drug binding to human serum albumin (HSA) has been characterized by a spin\u2010labeling and continuous\u2010wave (CW) EPR spectroscopic approach. Specifically, the contribution of functional groups (FGs) in a compound on its albumin\u2010binding capabilities is quantitatively described. Molecules from different drug classes are labeled with EPR\u2010active nitroxide radicals (spin\u2010labeled pharmaceuticals (SLPs)) and in a screening approach CW\u2010EPR spectroscopy is used to investigate HSA binding under physiological conditions and at varying ratios of SLP to protein. Spectral simulations of the CW\u2010EPR spectra allow extraction of association constants (<jats:italic>K<\/jats:italic><jats:sub>A<\/jats:sub>) and the maximum number (<jats:italic>n<\/jats:italic>) of binding sites per protein. By comparison of data from 23 SLPs, the mechanisms of drug\u2013protein association and the impact of chemical modifications at individual positions on drug uptake can be rationalized. Furthermore, new drug modifications with predictable protein binding tendency may be envisaged.<\/jats:p>","DOI":"10.1002\/chem.201601810","type":"journal-article","created":{"date-parts":[[2016,7,27]],"date-time":"2016-07-27T04:25:19Z","timestamp":1469593519000},"page":"12825-12838","source":"Crossref","is-referenced-by-count":27,"title":["Characterizing Active Pharmaceutical Ingredient Binding to Human Serum Albumin by Spin\u2010Labeling and EPR Spectroscopy"],"prefix":"10.1002","volume":"22","author":[{"given":"Till","family":"Hauenschild","sequence":"first","affiliation":[{"name":"Martin-Luther-Universit\u00e4t Halle-Wittenberg Institute of Chemistry  Von-Danckelmann-Platz 4 06120 Halle (Saale) Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rg","family":"Reichenwallner","sequence":"additional","affiliation":[{"name":"Martin-Luther-Universit\u00e4t Halle-Wittenberg Institute of Chemistry  Von-Danckelmann-Platz 4 06120 Halle (Saale) Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Volker","family":"Enkelmann","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Polymer Research  Ackermannweg 10 55128 Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6066-7099","authenticated-orcid":false,"given":"Dariush","family":"Hinderberger","sequence":"additional","affiliation":[{"name":"Martin-Luther-Universit\u00e4t Halle-Wittenberg Institute of Chemistry  Von-Danckelmann-Platz 4 06120 Halle (Saale) Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,7,27]]},"reference":[{"key":"e_1_2_6_1_1","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/12.6.439"},{"key":"e_1_2_6_2_1","first-page":"76","volume-title":"All about Albumin: Biochemistry Genetics, and Medical Applications: 3: Ligand Binding by Albumin","author":"Peters Th.","year":"1995"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2006.08.015"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/358209a0"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1107\/S174430910706770X"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-27-7-1012"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2005.07.075"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2013.04.031"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp3069877"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037468"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp709809b"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.4158"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2006.06.028"},{"key":"e_1_2_6_14_1","unstructured":"T. Hauenschild Spinmarkierung pharmazeutischer Wirkstoffe sowie deren Bindungseigenschaften an Serum Albumin vom Menschen Diploma Thesis Johannes Gutenberg University Mainz 2013; published by MPG.PuRe:http:\/\/hdl.handle.net\/11858\/00-001M-0000-0015-1BD8-0."},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5CP03583J"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0301-4622(84)85007-3"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-9084(78)80016-9"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2795(77)90286-0"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/oso\/9780198506348.001.0001"},{"key":"e_1_2_6_20_1","unstructured":"K. M\u00fcnnemann D. Hinderberger Physics Chemistry Biology and Medicine: Spotlight on the Spin Research Report2011 MPI-P Mainz Nr. 1179941."},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201003495"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201003495"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmr.2011.03.003"},{"key":"e_1_2_6_23_1","first-page":"183","volume-title":"Spin Labeling: Theory and Applications: The Chemistry of Spin Labels, Vol. 1","author":"Gaffney B. J.","year":"1976"},{"key":"e_1_2_6_24_1","first-page":"251","volume-title":"Biol. Magn. Reson.: Spin Labeling: The Next Millennium, Vol. 14","author":"Feix J. B.","year":"1998"},{"key":"e_1_2_6_25_1","first-page":"2439","volume-title":"Encyclopedia of Biophysics (S\u2013Z): Spin-Labeling EPR of Proteins: Dynamics and Water Accessibility of Spin-Label Side Chains, Vol. 5","author":"Bordignon E.","year":"2013"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11120-009-9490-7"},{"key":"e_1_2_6_27_1","first-page":"427","volume-title":"Protein Interactions: Site-Directed Spin Labeling and Electron Paramagnetic Resonance (EPR) Spectroscopy: A Versatile Tool to Study Protein\u2013Protein Interactions","author":"Klare J. P."},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/bm301531c"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0045681"},{"key":"e_1_2_6_30_1","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/S0021-9258(19)70053-2","volume":"256","author":"Cheng S.-Y.","year":"1981","journal-title":"J. Biol. Chem."},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.197805221"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.19780900718"},{"key":"e_1_2_6_32_1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1002\/0470858451.ch6","volume-title":"Fluxional Organometallic and Coordination Compounds: Dynamics by EPR: Picosecond to Microsecond Time Scales","author":"van Doorslaer S.","year":"2004"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-895X(25)10691-3"},{"key":"e_1_2_6_34_1","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1016\/S0026-895X(25)10855-9","volume":"12","author":"Sudlow G.","year":"1976","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmr.2005.08.013"},{"key":"e_1_2_6_36_1","first-page":"1","volume-title":"Biol. Magn. Reson.: Spin Labeling: Theory and Applications, Vol. 8","author":"Schneider D. J.","year":"1989"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1949.tb27297.x"},{"key":"e_1_2_6_38_1","first-page":"421","volume-title":"Lehninger Principles of Biochemistry: Box 12\u20131 Methods: Scatchard Analysis Quantifies the Receptor\u2013Ligand Interaction","year":"2008"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)36723-7"},{"key":"e_1_2_6_40_1","first-page":"115","volume-title":"Spin Labeling II: Theory and Applications: New Aspects of Nitroxide Chemistry, Vol. 2","author":"Keana J. F. W.","year":"1979"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/9783527621743"},{"key":"e_1_2_6_42_1","volume-title":"Nitroxide Spin Labels: Reactions in Biology and Chemistry","author":"Kocherginsky N.","year":"1995"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.99.2.167"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmra.1995.1169"},{"key":"e_1_2_6_45_1","volume-title":"The Weak Hydrogen Bond in Structural Chemistry and Biology","author":"Desiraju G. R.","year":"1999"},{"key":"e_1_2_6_46_1","volume-title":"CRC Handbook of Tables for Organic Compound Identification","year":"1967"},{"key":"e_1_2_6_47_1","first-page":"978","volume-title":"Springer Ser. Chem. Phys.: Spin Exchange: Principles and Applications in Chemistry and Biology, Vol. 8","year":"1980"},{"key":"e_1_2_6_48_1","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1093\/clinchem\/40.3.435","volume":"40","author":"Vieth R.","year":"1994","journal-title":"Clin. Chem."},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj1790413"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(84)90063-3"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr0500105"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)40727-8"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03245784"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2011.06.013"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7270.2008.00437.x"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmr.1167"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2014.11.012"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.044"},{"key":"e_1_2_6_59_1","first-page":"57","volume":"37","author":"Kragh-Hansen U.","year":"1990","journal-title":"Dan. Med. Bull."}],"container-title":["Chemistry \u2013 A European Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fchem.201601810","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chem.201601810","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T15:28:19Z","timestamp":1760282899000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/chem.201601810"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,27]]},"references-count":61,"journal-issue":{"issue":"36","published-print":{"date-parts":[[2016,8,26]]}},"alternative-id":["10.1002\/chem.201601810"],"URL":"https:\/\/doi.org\/10.1002\/chem.201601810","archive":["Portico"],"relation":{},"ISSN":["0947-6539","1521-3765"],"issn-type":[{"value":"0947-6539","type":"print"},{"value":"1521-3765","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,27]]}}}