Elucidation of the human serum albumin (HSA) binding site for the Cu-PTSM and Cu-ATSM radiopharmaceuticals

Abstract

The Cu-PTSM (pyruvaldehyde bis(N 4 -methylthiosemicarbazonato)copper(II)) and Cu-ATSM (diacetyl bis(N 4 -methylthiosemicarbazonato)copper(II)) radiopharmaceuticals exhibit strong, species-dependent binding to human serum albumin (HSA), while Cu-ETS (ethylglyoxal bis(thiosemicarbazonato)copper(II)) appears to only exhibit non-specific binding to human and animal serum albumins. This study examines the structural basis for HSA binding of Cu-PTSM and Cu-ATSM via competition with drugs having known albumin binding sites. Warfarin, furosemide, ibuprofen, phenylbutazone, benzylpenicillin, and cephmandole were added to HSA solutions at drug:HSA mole ratios from 0 to 8:

Species-dependent binding of new synthesized bicalutamide analogues to albumin by optical biosensor analysis

“…S3). These data are in good agreement with literature values obtained with different techniques [32][33][34]. The same experiment was repeated several times on the same RSA sensor chip, and the data were also confirmed by using the second RSA immobilized chip.…”

“…Also in this case (S)-warfarin was used as reference to check the dependability of the RSA sensor chip (see Section 3.3) [32][33][34].…”

Spectroscopic investigation of the interaction between thiourea-zinc complex and serum albumin

“…Thus, the interaction between drugs and albumins attracted much attention among bio-scientists, chemists and therapeutists [2][3][4]. Thiourea derivatives were extensively used in sterilization and as an antibacterial agent [5][6][7][8][9][10].…”

Cu(II) bis(thiosemicarbazone) radiopharmaceutical binding to serum albumin: further definition of species dependence and associated substituent effects

“…These uncharged square-planar copper(II) chelates share rigid π-conjugated ligand backbones, and differ only in various peripheral substitutions at the imine carbon, and terminal amine nitrogen, locations (Figure 2 and Tables 1 and 2). The high-affinity HSA binding of Cu-PTSM and Cu-ATSM appears [3] to occur in the well characterized IIA subdomain that is also responsible for binding the drugs warfarin and furosemide, among others [6-10]. …”