Potansiyel karbonik anhidraz I ve II inhibitör keşfi: D-Penisilamin türevleri

Year 2024, Volume: 14 Issue: 1, 274 - 282, 15.03.2024

Işıl Nihan Korkmaz

https://doi.org/10.17714/gumusfenbil.1359988

Abstract

Protein yapısına katılmayan bir aminoasit türevi olan penisilamin; bir karboksilik asit, bir tiyol ve aminden oluşan üç işlevli bir organik moleküldür. Başta Wilson hastalığı olmak üzere birçok hastalığın tedavisinde kullanılan D-Penisilamin (PEN-1), N-Asetil-D-Penisilamin (PEN-2) ve D-Penisilamin disülfit (PEN-3) in vitro koşullarda karbonik anhidraz I ve II (hCA I, hCA II) izoezimleri üzerindeki inhibisyon etkileri araştırıldı. İnsan eritrosit hücrelerinden hCA I, hCA II enzimleri izole edildi. Saflaştırılan her iki enzimin D-Penisilamin ve türevleri tarafından etkili bir şekilde inhibe edildiği belirlendi. PEN-1, PEN-2 ve PEN-3 moleküllerinin IC50 değerleri hCA I için sırasıyla 387.21; 407.49 ve 106.75 µM, hCA II için sırasıyla 563.72; 364.87 ve 136.91 µM olarak hesaplandı. Bütün moleküller için inhibisyon tipi her iki enzimde de yarışmalı inhibisyon olarak belirlendi.

Keywords

Afinite kromatografisi, İnhibisyon, Karbonik anhidraz, Penisilamin

Discovery of potential carbonic anhydrase I and II inhibitors: D-Penicillamine derivatives

Abstract

Penicillamine, an amino acid derivative that does not participate in the protein structure, is a trifunctional organic molecule composed of a carboxylic acid, a thiol, and an amine. D-Penicillamine (PEN-1), N-Acetyl-D-Penicillamine (PEN-2) and D Penicillamine disulfide (PEN-3), which are used in the treatment of many diseases, especially Wilson's disease, are produced by carbonic anhydrase I and II (hCA I) in vitro. Inhibition effects on hCA II) isoenzymes were investigated. hCA I, hCA II enzymes were isolated from human erythrocyte cells. It was determined that PEN-1, PEN-2, and PEN-3 effectively inhibited both purified enzymes. The IC50 values of PEN-1, PEN-2, and PEN-3 molecules were calculated to be 387.21, 407.49, and 106.75 µM for hCA I, 563.72 364.87, and 136.91 µM for hCA II, respectively. The inhibition type for all molecules was determined as competitive inhibition in both enzymes.

Keywords

Affinity chromatography, Inhibition, Carbonic anhydrase, Penicillamine

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