التفاصيل البيبلوغرافية
| العنوان: |
A synthetic mimic of phosphodiesterase type 5 based on corona phase molecular recognition of single-walled carbon nanotubes |
| المؤلفون: |
Dong, Juyao, Lee, Michael A, Rajan, Ananth Govind, Rahaman, Imon, Sun, Jessica H, Park, Minkyung, Salem, Daniel P, Strano, Michael S |
| المساهمون: |
Massachusetts Institute of Technology. Department of Chemical Engineering |
| المصدر: |
PNAS |
| بيانات النشر: |
Proceedings of the National Academy of Sciences |
| سنة النشر: |
2021 |
| المجموعة: |
DSpace@MIT (Massachusetts Institute of Technology) |
| الوصف: |
© 2020 National Academy of Sciences. All rights reserved. Molecular recognition binding sites that specifically identify a target molecule are essential for life science research, clinical diagnoses, and therapeutic development. Corona phase molecular recognition is a technique introduced to generate synthetic recognition at the surface of a nanoparticle corona, but it remains an important question whether such entities can achieve the specificity of natural enzymes and receptors. In this work, we generate and screen a library of 24 amphiphilic polymers, preselected for molecular recognition and based on functional monomers including methacrylic acid, acrylic acid, and styrene, iterating upon a poly(methacrylic acid-co-styrene) motif. When complexed to a single-walled carbon nanotube, some of the resulting corona phases demonstrate binding specificity remarkably similar to that of phosphodiesterase type 5 (PDE5), an enzyme that catalyzes the hydrolysis of secondary messenger. The corona phase binds selectively to a PDE5 inhibitor, Vardenafil, as well as its molecular variant, but not to other potential off-target inhibitors. Our work herein examines the specificity and sensitivity of polymer “mutations” to the corona phase, as well as direct competitions with the native binding PDE5. Using structure perturbation, corona surface characterization, and molecular dynamics simulations, we show that the molecular recognition is associated with the unique three-dimensional configuration of the corona phase formed at the nanotube surface. This work conclusively shows that corona phase molecular recognition can mimic key aspects of biological recognition sites and drug targets, opening up possibilities for pharmaceutical and biological applications. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| Relation: |
Proceedings of the National Academy of Sciences of the United States of America; https://hdl.handle.net/1721.1/135296 |
| الاتاحة: |
https://hdl.handle.net/1721.1/135296 |
| Rights: |
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. |
| رقم الانضمام: |
edsbas.39B1DD7F |
| قاعدة البيانات: |
BASE |