INVESTIGADORES
FIDELIO Gerardo Daniel
artículos
Título:
Binding of the highly toxic tetracycline derivative, anhydrotetracycline, to bovine serum albumin
Autor/es:
BURGOS I.,; FERNANDEZ R.A.; CELEJ, M.S.; FIDELIO G.D.; DASSIE SA.
Revista:
BIOL. PHARM. BULL.
Editorial:
PHARMACEUTICAL SOC JAPAN
Referencias:
Año: 2011
ISSN:
0918-6158
Resumen:
Tetracycline (TC) derivatives are
extensively used as antibiotics in human and animal medicine and, very
recently, they have been screened as anti-amyloidogenic drugs.
Anhydrotetracycline (AHTC) is one of the major degradation products of TC that
has been linked to several side effects of the drug. We evaluated the
interaction of AHTC with bovine serum albumin (BSA), one of the main carriers
of amphiphilic molecules in blood, using three complementary analytical
methods: fluorescence spectroscopy, isothermal titration calorimetry and
differential scanning calorimetry. AHTC bound to BSA with an association
constant in the order of 105 M-1. Drug binding was
enthalpically and entropically driven and seemed to involve hydrophobic
interactions. AHTC fluorescence enhancement and hypsochromic shifts observed
upon binding suggested a low-polarity location excluded from water for the
bound drug. Our data are useful for evaluating the biodisponibility of the
pharmacophore and the dynamic distribution of the toxic derivative.