Optimization of an α‐(Amino acid)‐<i>N</i>‐carboxyanhydride polymerization using the high vacuum technique: Examining the effects of monomer concentration, polymerization kinetics, polymer molecular weight, and monomer purity

Kowtoniuk, Robert A.; Pei, Tao; DeAngelo, Caitlin M.; Waldman, Jacob H.; Guidry, Erin N.; Williams, Jonathan; Garbaccio, R. M.; Barrett, Stephanie E.

doi:10.1002/pola.27132

Cited by 6 publications

(4 citation statements)

References 32 publications

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“…The typical polymer synthesis involved (1) synthesis of N -carboxyanhydride (NCA) of carbobenzyloxy (Cbz)- l -ornithine and Cbz- l -lysine amino acid monomers, (2) polymerization of peptide blocks from amino-terminated PVP and deprotection of polypeptide functional groups, and (3) ureido modification of polypeptide units of the block copolymer. The monomers Cbz- l -ornithine-NCA and Cbz- l -lysine-NCA were synthesized by phosgenation of protected peptides as described earlier , with a slight modification in purification and recrystallization steps as described below. Specifically, in a 100 mL round-bottom flask, Cbz- l -ornithine (1.75 g, 6.57 mmol) was mixed with THF (25 mL) at 25 °C for 30 min.…”

Section: Methodsmentioning

confidence: 99%

Upper Critical Solution Temperature Layer-by-Layer Films of Polyamino acid-Based Micelles with Rapid, On-Demand Release Capability

2017

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Here, we report on upper critical solution temperature (UCST)-type polyamino acid-based block copolymer assembled in a layer-by-layer system with a natural polyphenol. The UCST-type block copolymer, polyvinylpyrrolidone-b-polyureido(ornithine-co-lysine) (PVP-b-PUOL), was synthesized via ring opening polymerization followed by postpolymerization functionalization with ureido groups. PVP-b-PUOL exhibited UCST behavior that was controlled by both molecular weight and ornithine-to-lysine ratio. Importantly, PVP-b-PUOL with a UCST of 33 °C assembled into block copolymer micelles below UCST and dissociated above UCST, yet this behavior was not repeatable in solution due to β-sheet formation and large-scale aggregation. To overcome this limitation, UCST micelles (UCSTMs) were deposited within layer-by-layer (LbL) films via hydrogen bonding with tannic acid (TA). Significantly, the assembled TA/UCSTM films stabilized the micelles from desorption while maintaining their morphology and prevented β-sheet formation even after continuous exposure to 40 °C for 7 days. Moreover, these films demonstrated repeatable swelling−deswelling for up to five temperature cycles from 25 to 40 °C. The thermo-switchable hydrophobicity of micellar cores was used for trapping of a model active molecule, pyrene, and its on−off temperature-controlled release, demonstrating the potential of TA/UCSTM films for controlled delivery of active molecules.

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Section: Methodsmentioning

confidence: 99%

Upper Critical Solution Temperature Layer-by-Layer Films of Polyamino acid-Based Micelles with Rapid, On-Demand Release Capability

2017

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“…Poly( l -lysine), also known as alpha poly( l -lysine) or PLL, is one of the first nucleic acid carriers reported back in 1989. PLL can be synthesized by a living polymerization of N -carboxyanhydrides (NCA), which provides narrow chain length distributions and the ability to obtain high molecular weight poly(peptide) polymers . Various molecular weights ranging from 500 Da to more than 100 kDa of PLL are commercially available. , Among them, PLL ranging from 2.4 to ∼30 kDa have been exploited for siRNA delivery, and PLL with the molecular weight >70 kDa is mainly recommended for enhancing cell adhesion to solid surface .…”

Section: Poly(l-lysine) In Rna Deliverymentioning

confidence: 99%

Peptides Used in the Delivery of Small Noncoding RNA

2014

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RNA interference (RNAi) is an endogenous process in which small noncoding RNAs, including small interfering RNAs (siRNAs) and microRNAs (miRNAs), post-transcriptionally regulate gene expressions. In general, siRNA and miRNA/miRNA mimics are similar in nature and activity except their origin and specificity. Although both siRNAs and miRNAs have been extensively studied as novel therapeutics for a wide range of diseases, the large molecular weight, anionic surface charges, instability in blood circulation, and intracellular trafficking to the RISC after cellular uptake have hindered the translation of these RNAs from bench to clinic. As a result, a great variety of delivery systems have been investigated for safe and effective delivery of small noncoding RNAs. Among these systems, peptides, especially cationic peptides, have emerged as a promising type of carrier due to their inherent ability to condense negatively charged RNAs, ease of synthesis, controllable size, and tunable structure. In this review, we will focus on three major types of cationic peptides, including poly(l-lysine) (PLL), protamine, and cell penetrating peptides (CPP), as well as peptide targeting ligands that have been extensively used in RNA delivery. The delivery strategies, applications, and limitations of these cationic peptides in siRNA/miRNA delivery will be discussed.

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“…As a consequence, any side groups of these macromolecules rely on the substituent of the corresponding amino acid or the functional NCA. As demonstrated by several articles, these techniques in combination with functional monomers such as protected NCAs based on lysine, aspartic acid, or glutamic acid (just to name a few) deliver cationic or anionic polymers. ,− …”

Section: Introductionmentioning

confidence: 99%

One-Pot Synthesis of Amino Acid-Based Polyelectrolytes and Nanoparticle Synthesis

2016

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In this manuscript, a biscyclic monomer with an epoxide and a thiolactone ring connected by a urethane bond is used for the synthesis of amino acid-functional polyelectrolytes. In a first step, lithium salts of amino acids react selectively with the thiolactone ring by ring-opening, formation of an amide bond, and a thiol group. In a second step and in the presence of a base a polymeric building block is formed by polyaddition of the thiolate to the epoxide ring. The reaction occurs at room temperature in water as solvent. The resulting polymeric building block has a poly(thioether urethane) backbone, with hydroxyl- and amino acid side groups; the connection of the amino acid to the backbone occurs by an amide bond. As proof of concept, a selected series of amino acids and derivatives of such is used: glycine, alanine, tyrosine, glutamic acid, ε-amino caproic acid (as a lysine surrogate), BOC-lysine-O-methyl ester, BOC-lysine, and the dipeptide carnosine. The resulting polymer building blocks with molecular weights of M = 1830-9590 g/mol are entirely based on both bio-based and biodegradable components. Exemplarily, using the lithium salts of glycine and lysine methyl ester, anionic and cationic polyelectrolyte building blocks are obtained. A mixture of the two polyelectrolyte solutions results in the formation of polyelectrolyte complexes (PECs). With decreasing concentration of the polyelectrolyte solutions, the radii of PECs decrease.

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Optimization of an α‐(Amino acid)‐N‐carboxyanhydride polymerization using the high vacuum technique: Examining the effects of monomer concentration, polymerization kinetics, polymer molecular weight, and monomer purity

Cited by 6 publications

References 32 publications

Upper Critical Solution Temperature Layer-by-Layer Films of Polyamino acid-Based Micelles with Rapid, On-Demand Release Capability

Upper Critical Solution Temperature Layer-by-Layer Films of Polyamino acid-Based Micelles with Rapid, On-Demand Release Capability

Peptides Used in the Delivery of Small Noncoding RNA

One-Pot Synthesis of Amino Acid-Based Polyelectrolytes and Nanoparticle Synthesis

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