Measurements of plasma protein binding – variety of experimental techniques
Authors
Marković, Olivera S.Konstantinović, Jelena M.
Cvijetić, Ilija
Amézqueta, Susana
Valko, Klara
Ràfols, Clara
Polović, Natalija
Šolaja, Bogdan A.
Verbić, Tatjana
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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.
Source:
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, 2017, 30-30Publisher:
- International Association of Physical Chemists
Funding / projects:
- The synthesis of aminoquinoline-based antimalarials and botulinum neurotoxin A inhibitors (RS-MESTD-Basic Research (BR or ON)-172008)
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Hemijski fakultet / Faculty of ChemistryTY - CONF AU - Marković, Olivera S. AU - Konstantinović, Jelena M. AU - Cvijetić, Ilija AU - Amézqueta, Susana AU - Valko, Klara AU - Ràfols, Clara AU - Polović, Natalija AU - Šolaja, Bogdan A. AU - Verbić, Tatjana PY - 2017 UR - http://cherry.chem.bg.ac.rs/handle/123456789/5959 AB - 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. PB - International Association of Physical Chemists C3 - 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 T1 - Measurements of plasma protein binding – variety of experimental techniques SP - 30 EP - 30 UR - https://hdl.handle.net/21.15107/rcub_cherry_5959 ER -
@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" }
Marković, O. S., Konstantinović, J. M., Cvijetić, I., Amézqueta, S., Valko, K., Ràfols, C., Polović, N., Šolaja, B. A.,& Verbić, T.. (2017). Measurements of plasma protein binding – variety of experimental techniques. in 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 International Association of Physical Chemists., 30-30. https://hdl.handle.net/21.15107/rcub_cherry_5959
Marković OS, Konstantinović JM, Cvijetić I, Amézqueta S, Valko K, Ràfols C, Polović N, Šolaja BA, Verbić T. Measurements of plasma protein binding – variety of experimental techniques. in 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. 2017;:30-30. https://hdl.handle.net/21.15107/rcub_cherry_5959 .
Marković, Olivera S., Konstantinović, Jelena M., Cvijetić, Ilija , Amézqueta, Susana, Valko, Klara, Ràfols, Clara, Polović, Natalija, Šolaja, Bogdan A., Verbić, Tatjana, "Measurements of plasma protein binding – variety of experimental techniques" in 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 (2017):30-30, https://hdl.handle.net/21.15107/rcub_cherry_5959 .