Technology development for the production of biobased products from biorefinery carbohydrates—the US Department of Energy’s “Top 10” revisited

The development of nonviral vectors for safe and efficient gene delivery has been gaining considerable attention recently. An ideal nonviral vector must protect the gene against degradation by nuclease in the extracellular matrix, internalize the plasma membrane, escape from the endosomal compartment, unpackage the gene at some point and have no detrimental effects. In comparison to viruses, nonviral vectors are relatively easy to synthesize, less immunogenic, low in cost, and have no limitation in the size of a gene that can be delivered. Significant progress has been made in the basic science and applications of various nonviral gene delivery vectors; however, the majority of nonviral approaches are still inefficient and often toxic. To this end, two nonviral gene delivery systems using either biodegradable poly(D,Llactide-co-glycolide) (PLG) nanoparticles or cell penetrating peptide (CPP) complexes have been designed and studied using A549 human lung epithelial cells. PLG nanoparticles were optimized for gene delivery by varying particle surface chemistry using different coating materials that adsorb to the particle surface during formation. A variety of cationic coating materials were studied and compared to more conventional surfactants used for PLG nanoparticle fabrication. Nanoparticles (~200 nm) efficiently encapsulated plasmids encoding for luciferase (80-90%) and slowly released the same for two weeks. After a delay, moderate levels of gene expression appeared at day 5 for certain positively charged PLG particles and gene expression was maintained for at least two weeks. In contrast, gene expression mediated by polyethyleneimine (PEI) ended at day 5. PLG particles were also significantly less

Nonviral Vectors for Gene Delivery

Synthetic Polymers from Sugar-Based Monomers

Nucleic acid drugs have great potential to treat many devastating aliments, but their application has been hindered by the lack of efficacious and nontoxic delivery vehicles. Here, a new library of poly(glycoamidoamine)s (D1−D4, G1−G4, and M1−M4) has been synthesized by polycondensation of esterified d-glucaric acid (D), dimethyl-meso-galactarate (G), and d-mannaro-1,4:6,3-dilactone (M) with diethylenetriamine (1), triethylenetetramine (2), tetraethylenepentamine (3), and pentaethylenehexamine (4). The stereochemistry of the carbohydrate hydroxyl groups and the number of amine units have been systematically changed in an effort to examine how the polymer chemistry affects the plasmid DNA (pDNA) binding affinity, the compaction of pDNA into nanoparticles (polyplexes), the material cytotoxicity, and the efficacy of nucleic acid delivery. The polymers with four secondary amines (D4, G4, and M4) between the carbohydrates were found to have the highest pDNA binding affinity and the galactarate polymers general...

Hydroxyl stereochemistry and amine number within poly(glycoamidoamine)s affect intracellular DNA delivery.

In this report, four new poly(d-glucaramidoamine)s (1−4) have been designed to lower the toxicity of conventional polymeric nucleic acid delivery vehicles by incorporating a carbohydrate comonomer within a polyethylenimine (PEI)-like backbone. Polymers 1−4 were synthesized via polycondensation of esterified d-glucaric acid and four different amine-containing comonomers [diethylenetriamine (1), triethylenetetramine (2), tetraethylenepentamine (3), and pentaethylenehexamine (4)] in methanol. Viscometry and NMR studies suggest that the polymers are mostly linear (for 1−4, the α value in the Mark−Houwink−Sakurada equation = 0.6−0.7), thus indicating that polymerization occurs predominantly through the primary amines with a low degree of branching off the secondary amines. Results of gel electrophoresis shift assays show that polymers 1−4 bind pDNA at N/P ratios of 5, 3, 2, and 2, respectively. Also, dynamic light scattering and TEM experiments indicate that 1−4 compact DNA into nanoparticles (polyplexes) betw...

New Poly(d-glucaramidoamine)s Induce DNA Nanoparticle Formation and Efficient Gene Delivery into Mammalian Cells

Convenient procedures are described for the preparation of hydroxylated nylons (polyhydroxypolyamides) from D-glucaric acid. The procedures, which do not require protection/deprotection of carbohydrate hydroxyl groups, can be used to make a variety of polymers with a range of properties from D-glucaric acid. Simple alcohol (e.g. methanol or ethanol) esterification mixtures of D-glucaric acid (from oxidation of D-glucose) were reacted with bis-primary diamines in a polar solvent, typically methanol, to produce the polyamides. D-Glucaric acid esterification mixtures contain varying amounts of dialkyl D-glucarate, alkyl D-glucarate 1,4-lactone, and alkyl D-glucarate 6,3-lactone

Hydroxylated nylons based on unprotected esterified D-glucaric acid by simple condensation reactions

Convenient procedures are described for the preparation of hydroxylated nylons (polyhydroxypolyamides) from D-glucaric acid The procedures, which do not require protection/deprotection of carbohydrate hydroxyl groups, can be used to make a variety of polymers with a range of properties from D-glucaric acid Simple alcohol (eg methanol or ethanol) esterification mixtures of D-glucaric acid (from oxidation of D-glucose) were reacted with bis-primary diamines in a polar solvent, typically methanol, to produce the polyamides D-Glucaric acid esterification mixtures contain varying amounts of dialkyl D-glucarate, alkyl D-glucarate 1,4-lactone, and alkyl D-glucarate 6,3-lactone

Hydroxylated Nylons Based on Unprotected Esterified D-Glucaric Acid by Simple Condensation Reactions.

Novel monomers are described which contain a glucaric acid unit linked through an amide bond formed between a carbonyl carbon of a D-glucaric acid and one of the amino nitrogens of a primary diamine as well as their alkali metal salts. These N-aminohydrocarbylene (or N-aminoheterohydrocarbylene)-D-glucaramidates may then be polymerized to form polyhydroxypolyamides and in particular stereoregular polyhydroxypolyamides.

Process for preparing poly (glucaramides)

Novel monomers are described which contain a glucaric acid unit linked through an amide bond formed between a carbonyl carbon of a D-glucaric acid and one of the amino nitrogens of a primary diamine as well as their alkali metal salts These N-aminohydrocarbylene (or N-aminoheterohydrocarbylene)-D-glucaramidates may then be polymerized to form polyhydroxypolyamides and in particular stereoregular polyhydroxypolyamides

Liang Chen

Papers

Hydroxylated nylons based on unprotected esterified D-glucaric acid by simple condensation reactions

Hydroxylated Nylons Based on Unprotected Esterified D-Glucaric Acid by Simple Condensation Reactions.

Process for preparing poly (glucaramides)

Glucaric acid monoamides and their use to prepare poly(glucaramides)