Useful synthetic method of polypeptides with well‐defined structure by polymerization of activated urethane derivatives of α‐amino acids

Yamada, Shuhei; Koga, Kayoko; Endō, Takeshi

doi:10.1002/pola.26052

Cited by 40 publications

(73 citation statements)

References 23 publications

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“…For instance, the polypeptide chain with a desired ratio of a reactive function, which is suitable for the thiol-ene reaction, could be useful for the connection of vast numbers of thiol-containing biomolecules and functional groups to main polypeptide chain. Therefore, we examined the copolymerization behavior with NPC-Cys(VBn) and NPC-Lys(Boc), synthesized according to a previous report, [23] depending on the same reaction condition as PCys(VBn) (feeding ratio of Figure S7 (Supporting Information), the integration of vinylic protons of styrene corresponds to 15% PCys(VBn) units in the main chain that are roughly consistent with a feeding ratio (Scheme 5).…”

Section: Resultsmentioning

confidence: 99%

“…N-Phenoxycarbonyl of lysine(Boc) (NPC-Lys(Boc)) was prepared according to the literature reported previously. [23] …”

Section: Methodsmentioning

confidence: 99%

“…[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.…”

mentioning

confidence: 99%

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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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Section: Resultsmentioning

confidence: 99%

“…N-Phenoxycarbonyl of lysine(Boc) (NPC-Lys(Boc)) was prepared according to the literature reported previously. [23] …”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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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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“…Tetrabutylammonium salts of amino acids also readily react with DPC to yield the corresponding urethane derivatives, U P (Scheme , Table ) . A wide range of functional groups are compatible with the process.…”

Section: Preparation and Utilization Of O‐phenylurethanes Of Amino Acidsmentioning

confidence: 99%

Well‐defined, environment‐friendly synthesis of polypeptides based on phosgene‐free transformation of amino acids into urethane derivatives and their applications

Endō

Sudo

2019

Polymer International

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In this study, both naturally occurring and artificial amino acids were successfully transformed into the corresponding urethane derivatives using diphenyl carbonate. The urethanes thus prepared could be efficiently cyclized into amino acid N‐carboxyanhydrides (NCAs) without the requirement of phosgene. In addition, the presence of primary amines converted the urethane derivatives into NCAs and initiated the ring‐opening polymerization of the in situ formed NCAs, allowing for the well‐defined synthesis of polypeptides. These polypeptides contained initiating ends functionalized by an amine‐derived residue and propagating ends bearing the reactive amino group. By precise control of the structures of the polypeptides, various polypeptide conjugates such as block copolymers and graft copolymers were successfully synthesized as designed, and their applications in antifouling coatings against proteins, drug delivery systems and biosensors were demonstrated. © 2019 Society of Chemical Industry

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“…[6][7][8] To generate a bioconjugation system with synthetic polymer and biomaterial through covalent linkage, the most common method is the carbodiimide-mediated coupling reaction. [16][17] Amino-rich polymerbased nanoparticles for imaging-guided drug delivery and therapy, 18 biological labelling application of protein by aminated luminescent nanoparticles, 19 polyamine conjugates in systematic in vivo short interfering RNA delivery therapeutics, 20 surface initiated living polymerization of Ncarboxyanhydride (NCA) to obtain polypeptides by grafting [21][22][23] are the other typical uses and numerous other studies remain. Other similar approaches based on chemical modification of primary amine groups to make them appealing different bioconjugation pathways.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, characterization and targeted cell imaging applications of poly(p-phenylene)s with amino and poly(ethylene glycol) substituents

et al. 2015

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A novel approach for bioconjugation associated with fluorescent conjugated polymer is demonstrated. For this purpose, a conjugated polymer, poly(p-phenylene) (PPP), with lateral substituents, namely primary amino groups and poly(ethylene glycol) (PEG) chains, as potential building block for polymer bioconjugates was synthesized and characterized. The synthesis was achieved through Suzuki polycondensation reaction in the presence of Pd(PPh3)4 catalyst by using independently prepared PEG and amino functional dibromo benzenes in conjunction with benzene diboronic acid. For the evaluation of the bioactive PPP labeled with folic acid (FA) as a potential targeted cell imaging probe, HeLa and A549 cancer cells were used. Cytotoxicity assay showed that the polymer was not toxic to the both cells. Additionally, the fluorescence images showed that, depending on the level of the FA receptors on the cell surfaces, the fluorescent intensity in HeLa cells was obviously higher than A549 cells when treated with FA conjugated PPP-NH2-g-PEG polymer. The resulting FA/PPP-NH2-g-PEG conjugate was successfully used as bioconjugate for targeting and specifically imaging of FA receptor positive HeLa human cervices cancer cells.

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Useful synthetic method of polypeptides with well‐defined structure by polymerization of activated urethane derivatives of α‐amino acids

Cited by 40 publications

References 23 publications

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

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

Well‐defined, environment‐friendly synthesis of polypeptides based on phosgene‐free transformation of amino acids into urethane derivatives and their applications

Synthesis, characterization and targeted cell imaging applications of poly(p-phenylene)s with amino and poly(ethylene glycol) substituents

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