A synthetic mimic of phosphodiesterase type 5 based on corona phase molecular recognition of single-walled carbon nanotubes

Abstract

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.

Carbon Nanomaterials (CNMs) and Enzymes: From Nanozymes to CNM-Enzyme Conjugates and Biodegradation

“…They have been derivatized with polyoxometallatebased metal-organic frameworks (MOFs) for the selective sensing of cysteine [324], or with copper complexes [325], MOFs [326], and NPs [327] to develop nanozymes. For this type of application, many types of metal NPs have been used [328][329][330], as well as polymers to mimic phosphodiesterases [331]. Peroxidase mimicry can be exerted by other CNMs as well, and for various uses.…”

Dendron-Polymer Hybrids as Tailorable Coronae of Single-Walled Carbon Nanotube

“…Recently, several approaches have emerged for producing libraries of amphiphilic linear copolymers and block-copolymers that can be used for suspending SWCNT for specific applications 31 . These include combinatorial high-throughput screening of a library of polymers, 25,27,28 high-throughput directed evolution, 32,33 reversible addition-fragmentation chain transfer polymerization, 34,35 and random peptide synthesis. 36,37 Nevertheless, challenges such as elaborated synthesis, multiple processing steps, or limited control over the final product, give rise to the need for novel approaches for generating a library of highly versatile amphiphilic polymers with a wide range of molecular structures and functions.…”

Dendron-Polymer Hybrids as Tailorable Coronae of Single-Walled Carbon Nanotube

“…Recently, several approaches have emerged for producing libraries of amphiphilic linear copolymers and block-copolymers that can be used for suspending SWCNT for specific applications 31 . These include combinatorial high-throughput screening of a library of polymers, 25,27,28 high-throughput directed evolution, 32,33 reversible addition-fragmentation chain transfer polymerization, 34,35 and random peptide synthesis. 36,37 Nevertheless, challenges such as elaborated synthesis, multiple processing steps, or limited control over the final product, give rise to the need for novel approaches for generating a library of highly versatile amphiphilic polymers with a wide range of molecular structures and functions.…”