Title: Investigation of The Binding Potential of Gadobutrol, Iohexol and Fluorescein Radiocontrast Agents to the TSH Receptor

Abstract: Radiopaque agents can affect the human body in different ways. The resulting reactions are simple allergic and anaphylactic reactions. If the potential of these agents to bind to different receptors is determined beforehand, precautions can be taken against the side effects that may occur in the future. The aim of this study is to investigate the binding potential of the active substances Fluorescein, Gadobutrol, Iohexol, which are frequently used in routine, to the TSH receptor with molecular docking. The conformational analysis of 3 drugs on TSH receptor surfaces was performed by molecular docking using Autodocktools program. First, the atomic center of the receptor was determined at the grid stage, and the XYZ center of the grid box was set to 9.524, 48.24 and 25.257 A, respectively, and the space gap was set to 0.5. Thus, a box was created in which the ligand can easily scan the entire surface. In the docking phase, a parameter file has been prepared and run for 100 conformation and 300 population size, accompanied by Lamarckian and Genetic Algorithms. The binding energies of fluorescein, gadobutrol and iohexol strengthen the possibility of spontaneous binding. However, when the inhibition concentrations are evaluated, it shows that fluorescein can more easily bind to the TSH receptor. Gadobutrol and iohexol are unlikely to reach these concentrations in the blood. This in vitro study demonstrates the potential for spontaneous binding of fluorescein, gadobutrol, and iohexol to the TSH receptor. Even if radiopaque drugs are used for diagnostic purposes, they may cause side effects by interacting with different receptors in the human body. Experimental studies are needed to confirm this possibility.

Keywords: TSH receptor; molecular docking; binding energy; fluorescein; gadobutrol; iohexol

Başlık: Gadobutrol, Iohexol ve Floresein Radyokontrast Ajanlarının TSH Reseptörüne Bağlanma Potansiyelinin Araştırılması

Özet: Radyoopak ajanlar insan vücudunu farklı şekillerde etkileyebilir. Ortaya çıkan reaksiyonlar basit alerjik ve anafilaktik reaksiyonlardır. Bu ajanların farklı reseptörlere bağlanma potansiyeli önceden belirlenmesi durumunda ileride oluşabilecek yan etkilere karşı önlem alınabilir. Bu çalışmanın amacı rutinde sıklıkla kullanılan Fluorescein, Gadobutrol, Iohexol etken maddelerinin moleküler kenetlenme ile TSH reseptörüne bağlanma potansiyelinin araştırılmasıdır. 3 ilacın TSH reseptör yüzeyleri üzerindeki konformasyonel analizi, Autodocktools programı kullanılarak moleküler yerleştirme ile yapıldı. İlk olarak grid aşamasında reseptörün atom merkezi belirlendi ve grid kutusunun XYZ merkezi sırasıyla 9.524, 48.24 ve 25.257 A olarak ayarlandı ve boşluk aralığı belirlendi. 0,5'e kadar. Böylece ligandın tüm yüzeyi kolayca tarayabileceği bir kutu oluşturuldu. Yerleştirme aşamasında, 100 konformasyon ve 300 popülasyon büyüklüğü için bir parametre dosyası hazırlanmış ve Lamarckian ve Genetik Algoritmalar eşliğinde çalıştırılmıştır. Floresein, gadobutrol ve ioheksolün bağlanma enerjileri, kendiliğinden bağlanma olasılığını güçlendirir. Ancak inhibisyon konsantrasyonları değerlendirildiğinde, floreseinin TSH reseptörüne daha kolay bağlanabildiğini göstermektedir. Gadobutrol ve ioheksolün kanda bu konsantrasyonlara ulaşması olası değildir. Bu in vitro çalışma, floresein, gadobutrol ve iohexol'ün TSH reseptörüne kendiliğinden bağlanma potansiyelini göstermektedir. Radyoopak ilaçlar tanı amaçlı kullanılsa bile insan vücudundaki farklı reseptörlerle etkileşerek yan etkilere neden olabilirler. Bu olasılığı doğrulamak için deneysel çalışmalara ihtiyaç vardır.

Anahtar kelimeler: TSH reseptörü; moleküler doking; bağlanma enerjisi; floresein; gadobutrol; iyoheksol

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