Molecularly imprinted nanoparticles (MINPs) as antibody mimics

This dissertation presents a simple but effective method for the design and synthesis of molecularly imprinted nanoparticles (MINPs) as antibody mimics. The MINPs resembled proteins in their water-solubility, discrete nanosized structure, and in their ability to contain hydrophobic binding pockets in the interior while maintaining a hydrophilic exterior by virtue of the sugar-derived ligands incorporated onto the surface during the post-functionalization. A variety of MINPs with guest-tailored and modifiable hydrophobic binding pockets were synthesized and their applications in biomimetic recognition, molecular sensing, and generation of plastic monoclonal antibodies investigated

Imprinted micelles for chiral recognition in water: shape, depth, and number of recognition sites

Chiral molecular recognition is important to biology, separation, and asymmetric catalysis. Because there is no direct correlation between the chiralities of the host and the guest, it is difficult to design a molecular receptor for a chiral guest in a rational manner. By cross-linking surfactant micelles containing chiral template molecules, we obtained chiral nanoparticle receptors for a number of 4-hydroxyproline derivatives. Molecular imprinting allowed us to transfer the chiral information directly from the guest to host, making the molecular recognition between the two highly predictable. Hydrophobic interactions between the host and the guest contributed strongly to the enantio- and diastereoselective differentiation of these compounds in water, whereas ion-pair interactions, which happened near the surface of the micelle, were less discriminating. The chiral recognition could be modulated by tuning the size and shape of the binding pockets

Molecularly Responsive Binding through Co-occupation of Binding Space: A Lock–Key Story

When two guest molecules co-occupy a binding pocket of a water-soluble host, the first guest could be used as a signal molecule to turn on the binding of the second. This type of molecularly responsive binding strongly depends on the size of the two guests and the location of the signal molecule

Protein-Mimetic, Molecularly Imprinted Nanoparticles for Selective Binding of Bile Salt Derivatives in Water

A tripropargylammonium surfactant with a methacrylate-terminated hydrophobic tail was combined with a bile salt derivative, divinyl benzene (DVB), and a photo-cross-linker above its critical micelle concentration (CMC). Surface-cross-linking with a diazide, surface-functionalization with an azido sugar derivative, and free-radical-core-cross-linking under UV irradiation yielded molecularly imprinted nanoparticles (MINPs) with template-specific binding pockets. The MINPs resemble protein receptors in size, complete water-solubility, and tailored binding sites in their hydrophobic cores. Strong and selective binding of bile salt derivatives was obtained, depending on the cross-linking density of the system

Molecularly imprinted nanoparticles (MINPs) as antibody mimics

This dissertation presents a simple but effective method for the design and synthesis of molecularly imprinted nanoparticles (MINPs) as antibody mimics. The MINPs resembled proteins in their water-solubility, discrete nanosized structure, and in their ability to contain hydrophobic binding pockets in the interior while maintaining a hydrophilic exterior by virtue of the sugar-derived ligands incorporated onto the surface during the post-functionalization. A variety of MINPs with guest-tailored and modifiable hydrophobic binding pockets were synthesized and their applications in biomimetic recognition, molecular sensing, and generation of plastic monoclonal antibodies investigated.</p

Polymeric Nanoparticle Receptors as Synthetic Antibodies for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

The wide usage and subsequent leakage of nonsteroidal anti-inflammatory drugs (NSAIDs) into the environment present an urgent need to create materials for selective binding of NSAID drugs, which are highly similar to one another in structure and functionality. Surface–core double-cross-linking of cationic micelles containing Naproxen or Indomethacin as the template yielded molecularly imprinted nanoparticles (MINPs) for these drugs. The nanoparticle receptors resembled water-soluble proteins in their hydrophilic exterior and hydrophobic core with guest-tailored binding pockets. Their binding selectivity for their templates over other NSAID analogues rivaled that of antibodies prepared through much lengthier procedures.Reprinted (adapted) with permission from ACS Biomaterials Science & Engineering 1 (2015): 425, doi:10.1021/acsbiomaterials.5b00042. Copyright 2015 American Chemical Society.</p

Imprinted micelles for chiral recognition in water: shape, depth, and number of recognition sites

Chiral molecular recognition is important to biology, separation, and asymmetric catalysis. Because there is no direct correlation between the chiralities of the host and the guest, it is difficult to design a molecular receptor for a chiral guest in a rational manner. By cross-linking surfactant micelles containing chiral template molecules, we obtained chiral nanoparticle receptors for a number of 4-hydroxyproline derivatives. Molecular imprinting allowed us to transfer the chiral information directly from the guest to host, making the molecular recognition between the two highly predictable. Hydrophobic interactions between the host and the guest contributed strongly to the enantio- and diastereoselective differentiation of these compounds in water, whereas ion-pair interactions, which happened near the surface of the micelle, were less discriminating. The chiral recognition could be modulated by tuning the size and shape of the binding pockets.This is a manuscript of an article published as Awino, Joseph K. and Yan Zhao. "Imprinted micelles for chiral recognition in water: shape, depth, and number of recognition sites." Organic & Biomolecular Chemistry 15, no. 22 (2017): 4851-4858. DOI: 10.1039/C7OB00764G. Posted with permission.</p

Protein-Mimetic, Molecularly Imprinted Nanoparticles for Selective Binding of Bile Salt Derivatives in Water

A tripropargylammonium surfactant with a methacrylate-terminated hydrophobic tail was combined with a bile salt derivative, divinyl benzene (DVB), and a photo-cross-linker above its critical micelle concentration (CMC). Surface-cross-linking with a diazide, surface-functionalization with an azido sugar derivative, and free-radical-core-cross-linking under UV irradiation yielded molecularly imprinted nanoparticles (MINPs) with template-specific binding pockets. The MINPs resemble protein receptors in size, complete water-solubility, and tailored binding sites in their hydrophobic cores. Strong and selective binding of bile salt derivatives was obtained, depending on the cross-linking density of the system.Reprinted (adapted) with permission from Journal of the American Chemical Society 135 (2013): 12552, doi:10.1021/ja406089c. Copyright 2013 American Chemical Society.</p

Sequence-Selective Binding of Oligopeptides in Water through Hydrophobic Coding

A general method for sequence-specific binding of peptides remains elusive despite decades of research. By creating an array of “hydrophobically coded dimples” on the surface of surface–core doubly cross-linked micelles, we synthesized water-soluble nanoparticle receptors to recognize peptides by the location, number, and nature of their hydrophobic side chains. Minute differences in the side chains could be distinguished, and affinities up to 20 nM were obtained for biologically active oligopeptides in water.This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of the American Chemical Society, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see DOI: 10.1021/jacs.6b12949. Posted with permission.</p