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Electrospray ionization mass spectrometry as a tool for determination of drug binding sites to human serum albumin by noncovalent interaction
Author(s) -
Benkestock Kurt,
Edlund PerOlof,
Roeraade Johan
Publication year - 2005
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.1967
Subject(s) - chemistry , human serum albumin , naproxen , digitoxin , electrospray ionization , plasma protein binding , chromatography , blood proteins , mass spectrometry , drug , serum albumin , albumin , binding site , biochemistry , pharmacology , medicine , digoxin , heart failure , alternative medicine , pathology
Most proteins in blood plasma bind ligands. Human serum albumin (HSA) is the main transport protein with a very high capacity for binding of endogenous and exogenous compounds in plasma. Many pharmacokinetic properties of a drug depend on the level of binding to plasma proteins. This work reports studies of noncovalent interactions by means of nanoelectrospray ionization mass spectrometry (nanoESI‐MS) for determination of the specific binding of selected drug candidates to HSA. Warfarin, iopanoic acid and digitoxin were chosen as site‐specific probes that bind to the main sites of HSA. Two drug candidates and two known binders to HSA were analyzed using a competitive approach. The drugs were incubated with the target protein followed by addition of site‐specific probes, one at a time. The drug candidates showed predominant affinity to site I (warfarin site). Naproxen and glyburide showed affinity to both sites I and II. The advantages of nanoESI‐MS for these studies are the sensitivity, the absence of labeled molecules and the short method development time. Copyright © 2005 John Wiley & Sons, Ltd.