Publication

Synthesis of cyclic peptide disulfide-PHPMA conjugates via sequential active ester aminolysis and CuAAC coupling

Harm-Anton Klok
2016
Journal Articles

Abstract

Cyclic peptide disulfides (CXC) are an important class of biomolecules. The conjugation of cyclic peptide disulfides to synthetic polymers, however, is often difficult due to the presence of the disulfide bond combined with other potentially reactive side chain amino acids, such as lysine. This report describes a general, protective group-free method for the conjugation of CXCs to synthetic polymers using a sequential active ester aminolysis and copper catalyzed azide-alkyne cycloaddition (CuAAC) strategy, which starts from a poly(pentafluorophenyl methacrylate) (PPFMA) precursor. This route not only allows the incorporation of CXCs, but can be further explored to attach additional amine containing molecules to generate multifunctional copolymers. Various CuAAC protocols have been evaluated to couple a small library of cyclic peptide disulfides to an alkyne bearing poly(N-(2-hydroxypropyl) methacrylamide) (PHPMA) copolymer. The use of Cu(II)SO4, THPTA, sodium ascorbate and aminoguanidine for the CuAAC coupling was found to be suitable to yield well-defined cyclic peptide disulfide-PHPMA conjugates as evidenced by H-1-NMR and SEC analyses.

Official source

https://infoscience.epfl.ch/entities/publication/2d552e33-25e2-4c1f-a28e-7bf8dce61c49

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Harm-Anton Klok
2016
Journal Articles

Abstract

Official source

https://infoscience.epfl.ch/entities/publication/2d552e33-25e2-4c1f-a28e-7bf8dce61c49

About this result

Related concepts (18)

Azide-alkyne Huisgen cycloaddition

The azide-alkyne Huisgen cycloaddition is a 1,3-dipolar cycloaddition between an azide and a terminal or internal alkyne to give a 1,2,3-triazole. Rolf Huisgen was the first to understand the scope of this organic reaction. American chemist Karl Barry Sharpless has referred to this cycloaddition as "the cream of the crop" of click chemistry and "the premier example of a click reaction". In the reaction above azide 2 reacts neatly with alkyne 1 to afford the product triazole as a mixture of 1,4-adduct (3a) and 1,5-adduct (3b) at 98 °C in 18 hours.

Click chemistry

In chemical synthesis, click chemistry is a class of simple, atom-economy reactions commonly used for joining two molecular entities of choice. Click chemistry is not a single specific reaction, but describes a way of generating products that follow examples in nature, which also generates substances by joining small modular units. In many applications, click reactions join a biomolecule and a reporter molecule. Click chemistry is not limited to biological conditions: the concept of a "click" reaction has been used in chemoproteomic, pharmacological, biomimetic and molecular machinery applications.

Bioorthogonal chemistry

The term bioorthogonal chemistry refers to any chemical reaction that can occur inside of living systems without interfering with native biochemical processes. The term was coined by Carolyn R. Bertozzi in 2003. Since its introduction, the concept of the bioorthogonal reaction has enabled the study of biomolecules such as glycans, proteins, and lipids in real time in living systems without cellular toxicity.

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