Electrospray ionization mass spectrometry as a tool for determination of drug binding sites to human serum albumin by noncovalent interaction
2005 (English)In: Rapid Communications in Mass Spectrometry, ISSN 0951-4198, E-ISSN 1097-0231, Vol. 19, no 12, 1637-1643 p.Article in journal (Refereed) Published
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 nanoE-SI-MS for these studies are the sensitivity, the absence of labeled molecules and the short method development time.
Place, publisher, year, edition, pages
2005. Vol. 19, no 12, 1637-1643 p.
PROTEIN-LIGAND COMPLEXES; ULTRAFILTRATION; COMPETITION; RESOLUTION; AFFINITY; ACID
IdentifiersURN: urn:nbn:se:kth:diva-8360DOI: 10.1002/rcm.1967ISI: 000229846800008ScopusID: 2-s2.0-20644463474OAI: oai:DiVA.org:kth-8360DiVA: diva2:13661
QC 201007052008-05-072008-05-072010-07-05Bibliographically approved