Polypeptides and 100 Years of Chemistry of α‐Amino Acid <i>N</i>‐Carboxyanhydrides

Kricheldorf, Hans R.

doi:10.1002/anie.200600693

Cited by 588 publications

(537 citation statements)

References 333 publications

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“…In the synthetic approaches, stepwise solid-phase polypeptide synthesis (SPPS) [45,46], native chemical ligation (NCL) [47] or ring opening polymerisation of α-amino-N-carboxyanhydrides (NCAs) [48][49][50] can be included. Those techniques are mainly based on the use of amino acids or their derivatives as monomers and are particularly useful in the design of hybrid architectures that combine sequences of peptidic and non-peptidic nature.…”

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: Polypeptide Design and Synthesismentioning

confidence: 99%

“…There is a growing interest in developing synthetic strategies that could overcome the limitations of the genetically encoded synthesis to produce polypeptides with similar control of size and uniformity [48][49][50]. Among the advantages of the synthetic approaches, the following can be pointed out:…”

Section: Synthetic Approachesmentioning

confidence: 99%

Peptide-Based Polymer Therapeutics

2014

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“…This method produces polypeptoid polymers bearing the corresponding amide and secondary amino chain ends through a nucleophilic ROP mechanism which has been widely studied for the polymerization of amino acid-derived NCAs using primary amine initiators. [43] The early studies was mostly focused on the polymerization of sarcosine-derived N-carboxyanhydride monomers (Me-NCA), [44][45][46][47][48][49][50][51][52][53][54][55] yielding the water-soluble poly(N-methyl glycine)…”

Section: Synthesis Of Linear Polypeptoidsmentioning

confidence: 99%

Polypeptoid polymers: Synthesis, characterization, and properties

et al. 2017

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Polypeptoids, a class of peptidomimetic polymers, have emerged at the forefront of macromolecular and supramolecular science and engineering as the technological relevance of these polymers continues to be demonstrated. The chemical and structural diversity of polypeptoids have enabled access to and adjustment of a variety of physicochemical and biological properties (eg, solubility, charge characteristics, chain conformation, HLB, thermal processability, degradability, cytotoxicity and immunogenicity). These attributes have made this synthetic polymer platform a potential candidate for various biomedical and biotechnological applications. This review will provide an overview of recent development in synthetic methods to access polypeptoid polymers with well-defined structures and highlight some of the fundamental physicochemical and biological properties of polypeptoids that are pertinent to the future development of functional materials based on polypeptoids. | I N TR ODU C TI ONPolypeptoids composed of N-substituted polyglycine backbones are structural mimics of polypeptides ( Figure 1). Because of N-substitution, polypeptoids lack stereogenic centers and hydrogen bonding interactions along the main chains, in sharp contrast to polypeptides.As a result, the global conformations of polypeptoids are strongly dependent on the N-substituent structures, giving rise to random coils or well-defined secondary structures [eg, polyproline I (PPI) helix [1][2][3][4][5][6] and R-sheets] [7][8][9][10][11][12] that are reminiscent of those of polypeptides. The polypeptoid backbone containing tertiary amide linkages is highly polar and hydrophilic. The physicochemical properties of polypeptoids can be tailored by the N-substituent structures, enabling control over the hydrophilicity and lipophilicity balance (HLB), charge characteristics, [13,14] backbone conformation, [1][2][3][4][5][6][7][8][9][10][11][12] solubility, [15][16][17][18][19][20] thermal and crystallization properties of the polypeptoids. [21][22][23][24] Without extensive hydrogen bonding, polypeptoids are thermally processable similar to conventional thermoplastics, [20][21][22][23][24] whereas polypeptides undergo thermal degradation before they can be melt-processed due to the extensive hydrogen bonding interactions. While polypeptoids exhibited enhanced proteolytic stability relative to peptides, [25,26] they can be oxidatively degraded under conditions that mimic tissue inflammation, [27] suggesting their potential in vivo uses as biodegradable materials.Recent advances in the controlled polymerization methods have enabled access to a suite of structurally well-defined polypeptoids with various N-substituent structures and molecular architectures, setting the stage for the future development of polypeptoid materials for various targeted applications. Several review articles on the synthesis, properties, and application of polypeptoids for biomedical or nonbiomedical uses have been published in recent years. [28][29][30][31][32] As a result, this...

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“…Traditionally, most polypeptide-containing materials have been prepared by ringopening polymerization of the corresponding α-amino acids of N-carboxyanhydrides (NCAs) which proceeded in the living nature of the polymerization that could form a polypeptide with precisely controlled molecular weight, well-defined terminal structure, and low polydispersity. [14,15] However, earlier attempts to achieve NCA synthesis involve either the use of hazardous reagents or multistep reactions such as phosgene, or lack sufficient monomer purity for polymerization. Moreover, the requirement www.advancedsciencenews.com www.mcp-journal.…”

Section: Introductionmentioning

confidence: 99%

Phosgene‐Free Synthesis of Poly(l‐cysteine) Containing Styrene Moiety as a Reactive Function

Akbulut

Yamada

Endō

2017

Macro Chemistry & Physics

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for extreme impurity-free conditions to achieve the polymerization without side reactions, the sensitive nature of NCA for heating, and moisture are major drawbacks of its production toward practical use and chemical modifications. Thus, research on the development of alternative procedures [16][17][18][19][20][21][22] to obtain polypeptides from nontoxic materials with high purity and stability through the development of new synthetic strategies is of great interest in this research area.Quite recently, we have developed a newly synthetic route for the production of NCAs and polypeptides where the intramolecular cyclization of activated urethane derivatives of α-amino acids followed by the ring-opening polymerization of the in situ formed NCA led to the production of polypeptides without the use and production of any toxic compounds. [23][24][25] In this synthetic method, these activated urethane derivatives were readily synthesized by a twostep procedure: (i) the transformation of α-amino acids into the corresponding ammonium salts and (ii) the smooth reaction of N-carbamylation of the salts with diphenyl carbonate (DPC) to afford the corresponding urethane compound. Therefore, polypeptides synthesis using the urethane derivative, which are stable for moisture or heating and available for storing several months at room temperature, is more feasible than traditional ring opening polymerization of highly reactive NCAs in aspect of potential applicability for the convenient preparation of various kinds of functional polypeptides.The side-chain modification of polypeptides is an important tool for creating therapeutic conjugates, generating novel protein constructs and probing natural systems. Research on the combination of some reactive groups with amino acids and the discovery of different initiator systems for NCA-based peptide synthesis have emerged as one of the most popular topics in the synthesis of unique macromolecular architectures in recent years. [26][27][28] However, the sensitive nature of NCAs derivatives only allows two fundamental routes for the preparation of sidechain-modified polypeptides: (i) the prepolymerization modification route where the modified amino acid can be converted to NCA derivatives and then polymerized and (ii) the postpolymerization modification route where a chemically reactive moiety bearing polypeptide on the side chain can react with various functional reagents. [24,29] Polypeptides A novel approach toward the synthesis of N-carboxyanhydride precursor available for postpolymerization modification has been developed through a phosgene-free method offering a safer and green way to obtain peptide monomers under exceptionally mild reaction conditions. The homo and co-polypeptide bearing a reactive styrene moiety are prepared through the polycondensation of N-phenoxycarbonyl derivative of 4-vinylbenzyl-l-cysteine (NPC-Cys(VBn)) with the elimination of phenol and CO 2 while varying the feed ratio to the primary amine initiator to give the corresponding polypeptides without any d...

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Polypeptides and 100 Years of Chemistry of α‐Amino Acid N‐Carboxyanhydrides

Cited by 588 publications

References 333 publications

Peptide-Based Polymer Therapeutics

Peptide-Based Polymer Therapeutics

Polypeptoid polymers: Synthesis, characterization, and properties

Phosgene‐Free Synthesis of Poly(l‐cysteine) Containing Styrene Moiety as a Reactive Function

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