Naslov
A thermodynamic characterization of oral chemotherapeutic drug imatinib binding to the human α1-acid glycoprotein using isothermal titration calorimetry

Autori
Kerep, Robert ; Šeba, Tino ; Gabričević, Mario

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, ostalo, znanstveni

Izvornik
Book of abstracts of the 6th Central and Eastern European Conference on Thermal Analysis and Calorimetry (CEEC-TAC6) and 15th Mediterranean Conference on Calorimetry and Thermal Analysis (Medicta2021) / Andrei Rotaru, Matko Erceg - Split, 2021, 135-135

ISBN
978-606-11-7861-2

Skup
6th Central and Eastern European Conference on Thermal Analysis and Calorimetry (CEEC-TAC) ; 15th Mediterranean Conference on Calorimetry and Thermal Analysis (MEDICTA)

Mjesto i datum
Split, Hrvatska, 20.07.2021. - 24.07.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
alfa-kiseli glikoprotein, imatinib, vezanje, ITC
(alpha-acid glycoprotein, imatinib, binding, ITC)

Sažetak
Binding of drugs to proteins influence their pharmacokinetic and pharmacodynamics action. In the blood, the drug is distributed in the body in the free form or bound to plasma protein. α1-acid glycoprotein (AGP, also known as orosomucoid) is an important plasma protein involved in the binding and transport of many drugs, particularly basic one such as imatinib (IMT), a selective tyrosine kinase inhibitor, successfully used for the treatment of chronic myelogenous leukaemia and gastrointestinal stromal tumors [1-2]. This research uses sensitive and modern isothermal titration calorimetry (ITC) technique for characterization of microscopic thermodynamic parameters that trigger the binding of drugs to AGP. ITC is a convenient and widely used experimental technique to directly measure released or absorbed heat during association processes such as protein-drug interaction and to quantitatively measure the binding affinity [3]. The main goal of this research is to quantitatively evaluate the interaction between imatinib mesylate and AGP to characterize the nature and forces underlying the formation of a protein-drug complex. The binding of basic drug imatinib displayed an exothermically driven binding interaction with AGP. Binding energy was guided by a combination of favorable (negative) enthalpy (ΔrH = –4.21 kcal/mol) and favorable (positive) entropy (ΔrS = 3.62 kcal/mol K) contribution to the Gibbs free energy (ΔrG = –7.82 kcal/mol) with association constant (KA = 17.6 x 10-2 μM-1). Enthalpy change is an important step in understanding the driving forces that characterize the protein-drug interaction information very much needed in the drug discovery process.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

POVEZANOST RADA