In Silico Design of Novel Mutant Anti-MUC1 Aptamers for Targeted Cancer Therapy

Brianda L. Santini, Matías Zúñiga-Bustos, Abraham Vidal-Limon, Joel B. Alderete, Sergio A. Águila, Verónica A. Jiménez

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


The transmembrane glycoprotein mucin 1 (MUC1) is an attractive tumor marker for cancer therapy and diagnosis. The nine amino acid extracellular epitope APDTRPAPG of this protein is selectively recognized by the S2.2 single-stranded DNA anti-MUC1 aptamer, which has emerged as a promising template for designing novel targeting agents for MUC1-directed therapy. In this work, 100 ns molecular dynamics (MD) simulations, MM/GBSA binding free energy calculations, and conformational analysis were employed to propose a novel prospective anti-MUC1 aptamer with increased affinity toward the MUC1 epitope resulting from the double mutation of the T11 and T12 residues with PSU and U nucleosides, respectively. The double mutant aptamer exhibits a tight interaction with the MUC1 epitope and adopts a groove conformation that structurally favors the intermolecular contact with the epitope through the intermediate T11-A18 region leaving the 3′ and 5′ ends free for further chemical conjugation with a nanocarrier or pharmaceutical. These results are valuable to gain understanding about the molecular features governing aptamer-epitope interactions and constitute a first key step for the design of novel aptamer-based nanocarriers for MUC1-targeted cancer therapy.

Original languageEnglish
Pages (from-to)786-793
Number of pages8
JournalJournal of Chemical Information and Modeling
Issue number2
Publication statusAccepted/In press - 1 Nov 2019

ASJC Scopus subject areas

  • General Chemistry
  • General Chemical Engineering
  • Computer Science Applications
  • Library and Information Sciences


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