@conference{
author = "Marković, Olivera S. and Konstantinović, Jelena M. and Cvijetić, Ilija and Amézqueta, Susana and Valko, Klara and Ràfols, Clara and Polović, Natalija and Šolaja, Bogdan A. and Verbić, Tatjana",
year = "2017",
abstract = "Drug molecules in vivo may be bound to proteins and lipids in plasma and/or in tissues, or
free (unbound) in diffusion among the aqueous environment of the blood and tissues.
Data from in vitro plasma protein binding experiments that determine the fraction of
protein-bound drug are frequently used in drug discovery [1].
Human plasma proteins contain around 40 % albumin (HSA), 1-acid glycoprotein (AGP) in
much lower concentration (1-3 %) and immunoglobulins [2]. Methods used for drug –
plasma protein binding (PPB) studies are numerous and can be divided into two main
groups: separation methods (enabling the calculation of binding parameters, i.e. the number
of binding sites and their respective affinity constants) and non-separation methods
(describing predominantly qualitative parameters of the ligand-protein complex) [3].
Sometimes, results of PPB measurements obtained by different techniques are not
consistent. High binding affinity to plasma proteins is not necessarily a crucial limiting
factor for further delivery of compound to the target organ [1]. As an example, we show
the study of the interactions between HSA/AGP and an “in-house” synthesized steroidal
derivative that showed remarkable inhibitory potency against BoNT/A holotoxin in mouse
embryonic stem cell derived motor neurons [4]. A variety of experimental techniques (ITC,
HPLC, spectrofluorimetry, FTIR, and equilibrium dialysis) were used and the results were
compared highlighting the advantages and disadvatages of various techniques.",
publisher = "International Association of Physical Chemists",
journal = "6th IAPC Meeting Sixth World Conference on Physico-Chemical Methods in Drug Discovery & Third World Conference on ADMET and DMPK, Zagreb, Croatia, September 4-7, 2017",
title = "Measurements of plasma protein binding – variety of experimental techniques",
pages = "30-30",
url = "https://hdl.handle.net/21.15107/rcub_cherry_5959"
}