Recent advances in glycopolypeptide synthesis

Kramer, Jessica R.; Deming, Timothy J.

doi:10.1039/c3py01081c

Cited by 63 publications

(72 citation statements)

References 125 publications

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“…Such functional groups are difficult to introduce onto polypeptides by other methods, and are useful for a variety of applications including binding to biomolecules, 23 synthesis of hybrid copolymers, 24 or mimicking biomineralization processes. 25 We reasoned that the inability to completely functionalize M polymers with bulky epoxides was simply due to crowding of neighboring groups on the polymer backbone preventing further functionalization.…”

Section: Glycosylation (Procedures C)mentioning

confidence: 99%

Versatile Synthesis of Stable, Functional Polypeptides via Reaction with Epoxides

Gharakhanian

Deming

2015

Biomacromolecules

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Methodology was developed for efficient alkylation of methionine residues using epoxides as a general strategy to introduce a wide range of functional groups onto polypeptides. Use of a spacer between epoxide and functional groups further allowed addition of sterically demanding functionalities. Contrary to other methods to alkylate methionine residues, epoxide alkylations allow the reactions to be conducted in wet protic media and give sulfonium products that are stable against dealkylation. These functionalizations are notable since they are chemoselective, utilize stable and readily available epoxides, and allow facile incorporation of an unprecedented range of functional groups onto simple polypeptides using stable linkages.

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Section: Glycosylation (Procedures C)mentioning

confidence: 99%

Versatile Synthesis of Stable, Functional Polypeptides via Reaction with Epoxides

Gharakhanian

Deming

2015

Biomacromolecules

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“…The polymerization of NCAs to give polypeptides was first reported over 100 years ago and has since been widely used for rapid, scalable polypeptide synthesis and investigated for production of protein mimics (14,15). For several decades, researchers have attempted to polymerize glycosylated NCA monomers to yield biomimetic glycopolypeptides (16)(17)(18). However, past efforts found that glycosylated Ser/Thr NCAs either could not be polymerized (19) or gave only highly polydisperse oligomeric peptides (20,21) not useful as mimics of highmolecular weight mucins.…”

Section: Significancementioning

confidence: 99%

“…It is important to note our final yields are for highly pure NCAs obtained by anhydrous chromatography, a method recently developed to purify NCAs that are low melting or otherwise difficult to crystallize (23). Previously reported glyco-Ser NCAs were purified only by precipitation (16)(17)(18)(19)(20) and likely contained impurities that undermined the polymerization process (23).…”

Section: Significancementioning

confidence: 99%

Chemically tunable mucin chimeras assembled on living cells

Kramer

Onoa

Bustamante

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Mucins are a family of secreted and transmembrane glycoproteins characterized by a massive domain of dense O-glycosylation on serine and threonine residues. Mucins are intimately involved in immunity and cancer, yet elucidation of the biological roles of their glycodomains has been complicated by their massive size, domain polymorphisms, and variable glycosylation patterns. Here we developed a synthetic route to a library of compositionally defined, high-molecular weight, dual end-functionalized mucin glycodomain constructs via N-carboxyanhydride polymerization. These glycopolypeptides are the first synthetic analogs to our knowledge to feature the native α-GalNAc linkage to serine with molecular weights similar to native mucins, solving a nearly 50-year synthetic challenge. Physical characterization of the mimics revealed insights into the structure and properties of mucins. The synthetic glycodomains were end-functionalized with an optical probe and a tetrazine moiety, which allowed site-specific bioorthogonal conjugation to an engineered membrane protein on live mammalian cells. This strategy in protein engineering will open avenues to explore the biological roles of cell surface mucins.

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“…Polypeptoids, an analogue of polypeptides, are widely used as biocompatible materials applied in drug delivery, gene engineering and self‐assembly researches . Ring‐opening polymerization (ROP) of N ‐substituted glycine N ‐carboxyanhydrides (NNCAs) is the most promising approach to prepare polypeptoids with high productivity .…”

Section: Introductionmentioning

confidence: 99%

Polymerization rate difference of N‐alkyl glycine NCAs: Steric hindrance or not?

Bai

Ling

2019

Biopolymers

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Polypeptoids synthesized from N‐substituted glycine N‐carboxyanhydrides (NNCAs) are widely applied in biological fields. The effect of side groups in NNCA polymerizations is a key to develop novel polypeptoids with complex topologies and constituents. In this work, density functional theory (DFT) calculations are employed to investigate the propagation of a series of alkyl substituted NNCAs with solvation model. According to both computational and experimental results, carbonyl addition is confirmed as rate determining step and steric hindrance is recognized as the major factor of low reactivity in β‐C branched NNCAs. However, in linear and γ‐C branched case, aggregation of side groups instead of bulkiness is considered responsible for low polymerization rate.

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Recent advances in glycopolypeptide synthesis

Cited by 63 publications

References 125 publications

Versatile Synthesis of Stable, Functional Polypeptides via Reaction with Epoxides

Versatile Synthesis of Stable, Functional Polypeptides via Reaction with Epoxides

Chemically tunable mucin chimeras assembled on living cells

Polymerization rate difference of N‐alkyl glycine NCAs: Steric hindrance or not?

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