Human serum albumin binding of novel antiretroviral nucleoside derivatives of AZT.

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Quevedo MA, Moroni GN, Brinon MC

Human serum albumin binding of novel antiretroviral nucleoside derivatives of AZT.

Biochem Biophys Res Commun. 2001 Nov 9;288(4):954-60.

PubMed ID

11689002 [ View in PubMed

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Abstract

The binding of novel nucleoside derivatives (2-7) to the Human Serum Albumin (HSA) was studied using zidovudine (AZT), as standard compound. The applicability of two different techniques to separate unbound drug from drug-protein complex was analyzed: the gel filtration and ultrafiltration methods. Ultrafiltration was found to be an adequate procedure for the separation of unbounded drug from the drug-protein complex. Incubation temperature ranging from 0 to 37 degrees C did not modify considerably the bound fractions. The same effects were observed as HSA concentration was modified. Binding assays of studied compounds to purified 1% (w/v) HSA at 0 degrees C, indicate that bound fraction of 2-7 ranges from 13 to 47%, exhibiting a higher affinity to HSA than AZT (12%), which would introduce some interesting improvements in their pharmacokinetic properties. In addition, by means of displacement studies using HSA site specific drugs such as diazepam and salicylate, it was determined that AZT binds to site I of the HSA molecule, by a mainly entropy driven process (DeltaS = 10.834 cal/mol degrees K), being these observations extensive to 2-7. Some structural basis to explain enhanced affinity of these novel derivatives was also established.

DrugBank Data that Cites this Article

Drug Carriers

Drug	Carrier	Kind	Organism	Pharmacological Action	Actions
Zidovudine	Serum albumin	Protein	Humans	No	Not Available	Details