title: Arsenic trioxide binding to serum proteins.
abstract: Arsenic trioxide (ATO) also known as Trisenox, is an anticancer chemotherapeutic drug which has been used in treating diagnosed and relapsed patients with acute promyelocytic leukemia (APL). Serum albumin is the most abundant of the proteins in blood plasma and is the major transporter for delivering several drugs in vivo. The current study was designed to evaluate the potential ability of human and bovine serum albumin for delivering arsenic trioxide. Therefore, interaction of arsenic trioxide with HSA and BSA was investigated in aqueous solution at physiological conditions using a constant protein concentration and various drug contents. FTIR and UV-Vis spectroscopic methods were used to analyze arsenic trioxide and protein binding modes, the binding constants and the effect of drug complexation on HSA and BSA stability and conformation. Results of this study showed that drug complexation altered protein conformation by major reduction of α-helix and increase of turn structure which is indicative of a partial protein destabilization. Structural analysis revealed that arsenic trioxide bind HSA and BSA with overall binding constants of KATO-HSA=1.07 (±0.01)×10(4) M(-1) and KATO-BSA=1.27(±0.02)×10(4) M(-1). It could be concluded that serum albumins can be considered as good carriers for delivering arsenic trioxide to target tissue.
authors: Department of Chemistry, IAU, Central Tehran Branch (IAUCTB), Tehran, Iran.
authors: Sara
authors: S
authors: Shooshtary
authors: Department of Chemistry, IAU, Central Tehran Branch (IAUCTB), Tehran, Iran.
authors: Sima
authors: S
authors: Behtash
authors: Department of Chemistry, IAU, Central Tehran Branch (IAUCTB), Tehran, Iran; Department of Dermatology, University of California, San Francisco, CA, USA. Electronic address: drshnafisi@gmail.com.
authors: Shohreh
authors: S
authors: Nafisi
mesh_terms: D000818:Animals; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000737:chemistry / Q000378:metabolism*; D002417:Cattle; D006801:Humans; D010087:Oxides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D001152:Arsenicals; D010087:Oxides; D012709:Serum Albumin; D012710:Serum Albumin, Bovine; D000077237:Arsenic Trioxide
keywords: Arsenic trioxide; Bovine serum albumin; FT-IR; Human serum albumin; UV–Vis spectroscopy