Joongho Moon

Abstract

Peptides are recognized as highly promising therapeutics due to their high selectivity, efficacy, and safety. Enormous research development efforts have been devoted to developing peptide therapeutics, and more than 170 peptides therapeutics are currently being evaluated in clinical trials. However, the major drawback of peptide therapeutics is their short plasma half-life. Dr. Moon has developed linker peptides/proteins for intracellularly delivering small molecules such as drugs, nucleic acids, and peptides, as well as proteins and other larger molecules. These linker peptides/proteins are made of plurality of oligo( amino acid)s or poly( amino acid)s, where the acid residues can bear one or more positively charged guanylurea units. Many hydrophilic or hydrophobic functional groups can then be introduced at the units via guanylurea chemistry to modulate the linker peptides/proteins properties. Their C and N terminals can also be functionalized with small molecules such as drugs, antibodies, targeting moieties, detectable entities, further tailoring the linker peptides/proteins to specific needs.

Benefit

Enhanced blood circulation time and peptide serum stabilityEnhanced intracellular drug delivery and specific targeting, and pharmacokinetics

Market Application

Drug deliveryDrug development

Abstract

Labeling and monitoring of biological substances and activities in live cells are crucial for understanding complex biological systems and can permit development of biological/biomedical sensors or therapeutic means for various diseases. Some techniques employ small fluorescent molecules for labeling and sensing cellular substances. Unfortunately, since these small molecular weight compounds often enter the cells through passive diffusion mechanisms, high concentrations are required, increasing the likeliness of non-specific labeling and cellular toxicity. Polymeric nanoparticles (NPs) can improve the limitation of concentration of small molecules; however, due to their high molecular weights, these nanoparticles are inefficient for labeling intracellular molecules and organelles.Researchers at FIU have been able to combine the intracellular targeting advantages of both small molecules and nanoparticles by creating conjugated polymer nanoparticles comprising poly(p-phenyleneethynylene)s (PPEs) having a flexible linker between a portion of phenylene units. The flexible linkers can be sites for biodegradability of the PPEs into relatively small oligomers. The polymers can be tailored to a specific application through the modulation of their physical, biological and optical properties by structural modifications of the rigid conjugated backbone and the pendant sidechains.

Benefit

Offers an efficient one-pot synthesis that saves time, regents and eliminates the need for multiple production stepsProvides a customizable, biocompatible, and biodegradable delivery systemAllows for controlled release of molecules at target site and specific labelling

Market Application

Imaging of live cells including disease cells and tissuesSensing and monitoring of biological events at targeted organellesTargeted in vivo drug/gene delivery

Publications

Chem. Commun., 2016,52, 4910-4913

Abstract

Fluorescent labelling of intracellular organelles, proteins, or nucleic acids (NAs) is an essential way of studying the structure and function of live cells. With their excellent photophysical and biophysical properties, conjugated polymers (CPs) and conjugated polymer nanoparticles (CPNs) are useful for labelling, sensing, and delivery of biological substances. However, relatively large molecular weights and broad molecular weight distributions of CP-based materials often limit their intracellular applications in live cells. Due to a smaller hydrodynamic volume, molecularly defined short conjugated oligomers (COs) appear to enter cells by fast diffusion through the cell membranes, whereas CPs and CPNs are most likely endocytosed and entrapped in endosomes or lysosomes. Despite their advantages, there are few examples of COs being used for fluorescent labelling applications in live cells. To combine the advantages of conjugated polymers (CPs) with more chromophores per molecule and conjugated oligomers (COs) with monodispersed molecular weights and fast cellular entry, the inventor has synthesized phenyleneethynylene macrocycles (PEMCs). The macrocycles are prepared by using imine coupling between aldehyde end-capped phenyleneethynylene (PE) trimer units and flexible diamines. For polycyclic macrocycles, the amine can be triamines or tetraamines. Because the equilibrium in the imine bond formation can be quantitatively shifted to thermodynamically favored products, the target macrocycles can be obtained in high yields without accompanying by-products.

Benefit

Can be obtained in high yields without accompanying byproductsExhibit fast cellular entry, RNA selectivity, and nontoxicity

Market Application

Visualization and imaging of cellular RNA using standard microscopy techniques

Publications

Moon et al. Phenyleneethynylene trimer-based rigid-flexible [2+2] macrocycles for nucleic acid labelling in live cells. Chem. Commun., 2019,55, 5930-5933

Abstract

This invention is a novel monomer design for the synthesis of poly-p-(phenyleneethynylene)s (PPE)-type polymers containing conjugated segments of well-defined length connected by flexible linkers. This has many applications including solar cell fabrications, chemical sensors, various light emitting devices, biological sensors, gene delivery, drug delivery, etc. Also, oligomers may be used for the investigation of processes governing the physical and photophysical properties of the corresponding larger, polydisperse polymeric materials. These polymers are also biocompatible and biodegradable. This synthetic approach is carried out in one step, eliminating the need for the traditional multi-step approaches which are very low yielding, time consuming, and costly.

Benefit

One step synthetic approach which eliminates low yielding, time consuming, costly approachesBiocompatible & biodegradable

Market Application

Solar cell fabricationsChemical sensorsBiological sensorsGene deliveryDrug deliveryVarious light emitting devicesTissues imagingMicroscopic imaging

Publications

Vokata, T., Twomey, M., Mendez, E., and Moon, J. H. (2015) Synthesis of biodegradable conjugated polymers with controlled backbone flexibility. J. Polym. Sci., Part A: Polym. Chem. 53, 1403– 1412, DOI: 10.1002/pola.27622

Abstract

Aromatic π-electron conjugated polymers (CPs) are innovative fluorescent materials that have a high potential as therapeutic carriers. Because of excellent photophysical properties, such as high brightness and sensing ability, and excellent biophysical properties, such as biocompatibility, nontoxicity, high cellular interaction, and ease of entry, CPs have been used for live cell and tissue imaging, biochemical sensing, and gene and drug delivery. Biodegradable CPs can be formed by introducing flexible degradable functional groups along the backbone of the CPs. Conventional method of synthesizing CPs with diverse functional group is tedious and problematic. In addition to intrinsic synthetic challenge of optimizing polymerization conditions for each monomer, the resulting CP with different functional group will have different molecular weight and polydispersity, which will influence their physical and biophysical behaviors. FIU inventors have synthesized modulated guanidine substituted polymer and modulated guanidine substituted nanoparticle with guanidine moieties. These polymers and nanoparticles can be prepared by direct amination of a N-Boc protected guanidine substituted conjugated polymer or nanoparticle, where an amine or alcohol is combined in solution or suspension with the protected conjugated polymer or nanoparticle and the resulting mixture is heated. The synthetic method can be applied to a wide range of nanoparticles, synthetic and natural polymers, as well as conjugated and non-conjugated polymers having a flexible backbone.

Benefit

Allows for the synthesize of structurally diverse polymers without tedious polymerization stepsProvides a catalyst free post polymerization technique to incorporate a variety of hydrophilic and hydrophobic functional groupProduces high yields of modulated CPs with enhanced cellular entry, modulated intracellular localization, and better siRNA delivery

Market Application

Drug and gene deliveryWater treatmentSensors

Publications

Ahmed MS , Dutta RK , Manandhar P , et al. A guanylurea-functionalized conjugated polymer enables RNA interference in ex vivo human airway epithelium. Chem Commun (Camb). 2019;55(54):7804-7807. doi:10.1039/c9cc02856k

Abstract

The design and synthesis of new nanomaterials that enhance or assist the passage of therapeutics across cellular membranes both in vitro and in vivo is of immense significance in research and therapy. Many drug candidates fail to advance clinically as they do not have the properties needed to cross biological membranes and reach their intracellular target. Additionally, poor pharmacokinetics, stability, and off-target effects leads to undesirable biological responses. Polymeric systems, specifically, cell-penetrating peptides (CPPs) and their synthetic mimics (CPPMs) offer hope for new therapeutic approaches and have played a vital role in the advancement of drug delivery technology. The synthesis of molecular transporters using ring-opening metathesis polymerization (ROMP) is advantageous due to its living polymerization character. ROMP polymers offer great benefits over other polymerization techniques such as controlled polymer length, low polydispersity index (PDI) and easy of copolymer design. Several groups have increased their efforts toward improving the transportation ability of guanidine-rich molecular transporters. To date, the main modification done to CPPs and their synthetic mimics have included the addition of hydrophobic moieties to the polymer sequence, however, the guanidine group itself has mostly been kept “untouched.â€쳌 Mono and di-alkylation of guanidine has resulted in decreased cellular uptake of CPPs and mimics, leading researchers in other directions.FIU inventors have expanded the field of guanidine-rich molecular transporters into systems with modified guanidines. Guanylureas, also referred to as amidinoureas, are moieties with extended hydrogen bonding capacity as compared to guanidine. Utilizing well-defined polymers, a function-oriented synthesis approach has been employed and the initial results demonstrate improved intracellular protein delivery using guanylurea functionalized molecular transporters.

Benefit

Allows for the synthesize of structurally diverse polymers without tedious polymerization stepsProvides a catalyst free post polymerization technique to incorporate a variety of hydrophilic and hydrophobic functional groupProduces high yields of modulated CPs with enhanced cellular entry, modulated intracellular localization, and better siRNA delivery

Market Application

Drug and gene deliveryWater treatmentSensors

Abstract

Antimicrobial drug resistance has emerged rapidly and thwarted treatment options, leading to prolonged illness, disability, and death. Despite considerable efforts to develop new antimicrobial drugs, many bacterial infections remain difficult to treat due to acquired drug resistance. Compared to small molecular antibiotics designed to interrupt the bacterial intracellular biochemical processes, antimicrobial polymers disrupt the membrane integrity, offering a promising strategy to overcome drug resistance. Bacteria have little chance of developing resistance mechanism against the physical disruption, which often leads to cell death.FIU inventors have developed a new class of linear polymers containing positively charged guanylurea backbones. Compared with most antimicrobial polymers with positively charged side chains, the new polymer design introduces both positive charge and hydrophobicity into the flexible polymer backbones.The initial structure−activity relationship studies demonstrate that poly-(guanylurea piperazine)s (PGU-Ps) exhibit excellent antimicrobial activity against different types of bacteria with high selectivity. The simplicity of polymerization without requiring any catalysts or specialized conditions, the availability of numerous commercial amines, and the biocompatible guanylurea functional groups are clear advantages over the existing materials. The new design concept provides a promising method toward the realization of potent antimicrobial polymers exhibiting high selectivity over mammalian cells and/or high specificity toward a target microorganism.

Benefit

Less toxic, more efficient and selective than low molecular weight antimicrobial agents Slows/inhibits the progress of drug-resistant microorganism strains because of the distinctive antimicrobial mechanism Overcomes antimicrobial resistance associated problems Provides a simplified synthesis that does not require any catalysts or specialized conditions Provides a simplified polymer architecture by linearly combining the key functional units along the backbone

Market Application

Antimicrobial coating for surgical instruments, medical devices, drugs, wound-dressings, textiles, and food packaging and storage

Publications

Ahmed MS, Annamalai T, Li X, et al. Synthesis of Antimicrobial Poly(guanylurea)s. Bioconjug Chem. 2018;29(4):1006-1009. doi:10.1021/acs.bioconjchem.8b00057