A controlled and versatile NCA polymerization method for the synthesis of polypeptides

Conejos‐Sánchez, Inmaculada; Duro‐Castaño, Aroa; Birke, Alexander; Barz, Matthias; Vicent, Marı́a J.

doi:10.1039/c3py00347g

Cited by 109 publications

(120 citation statements)

References 30 publications

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“…The recently reported use of primary amine tetrafluoroborate (BF 4 ) salts by Conejos-Sanchez et al [51,82] as an improvement of the Schlaad method represents a powerful alternative to the above-described methodologies, since the non-nucleophilicity of the BF 4 salts in contrast to the Cl counteranions cannot lead to initiation steps ( Figure 5). This newly reported strategy allows a multigram scale [83] polyglutamate synthesis with defined molecular weight (up to 800 units), low polydispersity (<1.2), controlled chain end functionality and adequate stereoselectivity and absence of any trace of toxic impurity to allow biomedical applications.…”

Section: Scheme 1 Ring-opening Polymerisation Of α-Amino Acid N-carbmentioning

confidence: 99%

“…Control on polymer chain length and stereochemistry have been one of the major challenges in synthetic approaches over the past years. However, recent reports have demonstrated how to overcome those limitations with precise controlled reactions followed by an adequate characterisation yielding to well-defined polypeptidic architectures [51].…”

Section: Polypeptide Design and Synthesismentioning

confidence: 99%

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Peptide-Based Polymer Therapeutics

2014

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Abstract:Polypeptides are envisaged to achieve a major impact on a number of different relevant areas such as biomedicine and biotechnology. Acquired knowledge and the increasing interest on amino acids, peptides and proteins is establishing a large panel of these biopolymers whose physical, chemical and biological properties are ruled by their controlled sequences and composition. Polymer therapeutics has helped to establish these polypeptide-based constructs as polymeric nanomedicines for different applications, such as disease treatment and diagnostics. Herein, we provide an overview of the advantages of these systems and the main methodologies for their synthesis, highlighting the different polypeptide architectures and the current research towards clinical applications.

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Section: Scheme 1 Ring-opening Polymerisation Of α-Amino Acid N-carbmentioning

confidence: 99%

Section: Polypeptide Design and Synthesismentioning

confidence: 99%

Peptide-Based Polymer Therapeutics

2014

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“…Polypeptides with significantly narrower molecular weight distributions were obtained as compared to polypeptide initiated by primary amine macroinitiator. Since chloride anion is known to be able to initiate the polymerization of NCA, a primary amine salt with a non-nucleophilic anion was used by Vicent et al [17]. They have prepared a series of primary amine tetrafluoroborate salts (R-NH 3 + BF 4 À ) and tested them as initiators.…”

Section: Polymerization Mechanismsmentioning

confidence: 99%

Ring-Opening Polymerization of N-Carboxyanhydrides for Preparation of Polypeptides and Polypeptide-Based Hybrid Materials with Various Molecular Architectures

Pahovnik

Hadjichristidis

2015

Anionic Polymerization

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Different synthetic approaches utilizing ring-opening polymerization of N-carboxyanhydrides for preparation of polypeptide and polypeptide-based hybrid materials with various molecular architectures are described. An overview of polymerization mechanisms using conventional (various amines) as well as some recently developed initiators (hexamethyldisilazane, N-heterocyclic persistent carbenes, etc.) is presented, and their benefits and drawbacks for preparation of polypeptides with well-defined chain lengths and chain-end functionality are discussed. Recent examples from literature are used to illustrate different possibilities for synthesis of pure polypeptide materials with different molecular architectures bearing various functional groups, which are introduced either by modification of amino acids, before they are transformed into corresponding Ncarboxyanhydrides, or by post-polymerization modifications using protective groups and/or orthogonal functional groups. Different approaches for preparation of polypeptide-based hybrid materials are discussed as well using examples from recent literature. Syntheses of simple block copolymers or copolymers with more complex molecular architectures (graft and star copolymers) as well as modifications of nanoparticles and other surfaces with polypeptides are described.

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“…[40] When ammonium salts with non-nucleophilic tetrafluoroborate anions are used as initiators, multigram scale polyglutamate with defined molecular weight (up to 800 units) and low polydispersity (<1.2) can be synthesized by the ROP of NCAs. [41] Many copolypeptides have been reported to be prepared by the NCA polymerization. [42][43][44][45] Especially, as a typical copolypeptide, Glatiramer Acetate (copolymer-1; Cop-1; Copaxone 1 ) has been approved as an effective treatment in relapsing multiple sclerosis (MS).…”

Section: Introductionmentioning

confidence: 99%

Poly(ornithine‐co‐arginine‐co‐glycine‐co‐aspartic Acid): Preparation via NCA Polymerization and its Potential as a Polymeric Tumor‐Penetrating Agent

Tang

Zhang

et al. 2015

Macromolecular Bioscience

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A novel random copolypeptide of ornithine, arginine, glycine, and aspartic acid [Poly(ornithine-co-arginine-co-glycine-co-aspartic acid), Poly(O,R,G,D)] has been prepared through ring-opening polymerization of N-δ-carbobenzoxy-l-ornithine N-carboxyanhydride [Orn(Cbz)-NCA)], l-glycine N-carboxyanhydride (Gly-NCA) and β-benzyl l-aspartate N-carboxyanhydride [Asp(Bn)-NCA], following by subsequent deprotection and guanidization. The structure of Poly(O,R,G,D) was confirmed by nuclear magnetic resonance (NMR) spectroscopy and gel permeation chromatography (GPC). Low cytotoxicity of Poly(O,R,G,D) was confirmed from MTT assay. The Poly(O,R,G,D) contain some internal sequences of RXXR (X = O, R, G, or D) that could be proteolytically cleaved to expose the cryptic CendR element and bind to Neuropilin-1. This would lead to vascular and tissue permeabilization. Therefore trypsin-cleaved Poly(O,R,G,D) increase the vascular leakage of Evans blue from dermal microvessels at the injection site in vivo skin permeability assay. The intratumoral injection of the Poly(O,R,G,D) significantly enhanced the concentration of cisplatin-loaded nanoparticles in MCF-7 solid tumors. These results show that Poly(O,R,G,D) could increase the vascular leakage and tissue penetration of nanoparticles in a solid tumor and can be used as a potential polymeric tumor-penetrating agent.

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A controlled and versatile NCA polymerization method for the synthesis of polypeptides

Cited by 109 publications

References 30 publications

Peptide-Based Polymer Therapeutics

Peptide-Based Polymer Therapeutics

Ring-Opening Polymerization of N-Carboxyanhydrides for Preparation of Polypeptides and Polypeptide-Based Hybrid Materials with Various Molecular Architectures

Poly(ornithine‐co‐arginine‐co‐glycine‐co‐aspartic Acid): Preparation via NCA Polymerization and its Potential as a Polymeric Tumor‐Penetrating Agent

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