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Dergiler / Journal of the Turkish Chemical Society Section A: Chemistry / 2026 / Volume: 2026 Issue: 2

Computational Analysis of Nucleotide Substitutions in a CD47 Aptamer: Structural and Energetic Insights

Sümeyye Altunok(The Ohio State University)0000-0002-9004-0617
Emre Can Buluz(EGE ÜNİVERSİTESİ)0000-0002-2491-4347
Ehed Muhammed Aymaz(ISTINYE UNIVERSITY)0009-0006-7337-1365
Sayfa
—
Yayın Tarihi
2026-07-28
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⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

These findings demonstrate that systematic computational mutagenesis is an effective strategy for optimizing aptamer performance and identifying high-affinity CD47-targeting candidates.

📌 3 Maddede Bu Makale

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Amaç & Hipotez:The Cluster of Differentiation 47 (CD47)–signal regulatory protein alpha (SIRPα) immune checkpoint is a key regulator of tumor immune evasion and a promising target in cancer immunotherapy.
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Temel Bulgular & Veri:To overcome the limitations of monoclonal antibodies, this study aimed to identify high-affinity nucleic acid aptamers targeting CD47.
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Sonuç & Katkı:These findings demonstrate that systematic computational mutagenesis is an effective strategy for optimizing aptamer performance and identifying high-affinity CD47-targeting candidates.
🔬Tür:Research Article
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:CD47 aptamer · in silico mutagenesis · MM/PBSA analysis

Abstract

The Cluster of Differentiation 47 (CD47)–signal regulatory protein alpha (SIRPα) immune checkpoint is a key regulator of tumor immune evasion and a promising target in cancer immunotherapy. To overcome the limitations of monoclonal antibodies, this study aimed to identify high-affinity nucleic acid aptamers targeting CD47. A systematic single-nucleotide mutagenesis workflow was performed on a known CD47-binding DNA aptamer to generate 270 single-point variants, enabling unbiased evaluation of each nucleotide position. The variants were first screened for structural stability, yielding 81 structurally stable candidates. These candidates were then subjected to molecular docking against CD47, and 45 variants showed improved docking scores compared with the native aptamer. The docking score improved from −226.07 for the native aptamer to −301.94 for the best-performing variant. Based on structural stability and docking performance, the ten top-ranked candidates were selected for molecular dynamics simulations. These variants exhibited improved conformational stability, as reflected by lower root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) values and increased hydrogen bonding, with Seq198 and Seq262 showing the most stable profiles. Binding free energy calculations confirmed improved affinity. The native aptamer exhibited a ΔTOTAL of −97.16 kcal/mol, whereas Seq198 (−173.13 kcal/mol), Seq244 (−152.35 kcal/mol), and Seq112 (−147.19 kcal/mol) showed markedly stronger binding. Seq198 emerged as the most promising candidate. These findings demonstrate that systematic computational mutagenesis is an effective strategy for optimizing aptamer performance and identifying high-affinity CD47-targeting candidates.

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Bu Makaleye Atıf Yap

Altunok, S., Buluz, E. C., Aymaz, E. M. (2026). Computational Analysis of Nucleotide Substitutions in a CD47 Aptamer: Structural and Energetic Insights. Journal of the Turkish Chemical Society Section A: Chemistry, Volume: 2026 Issue: 2. https://doi.org/10.18596/jotcsa.1892713

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