More than add-on: chemoselective reactions for the synthesis of functional peptides and proteins

Schumacher, Dominik; Hackenberger, Christian P. R.

doi:10.1016/j.cbpa.2014.09.018

Cited by 87 publications

(54 citation statements)

References 62 publications

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“…6,7,10 However, the AF peptide contains three hydrophobic amino acids (tryptophan, phenylalanine, and isoleucine) that lead to poor water solubility, thus restricting their applicability. [11][12][13] To obtain a more biologically active and effective target for the inhibition of angiogenic peptides, a synthetic peptide anti-Flt1-ES2 (IVRRADRAAVPGGGGGNQWFI, ES2-AF) was prepared by solid-phase synthesis. Polypeptides and protein drugs are easily degraded in plasma, tissues, and cells by various metabolic enzymes in the body, resulting in their poor stability and a short half-life in vivo.…”

Section: Introductionmentioning

confidence: 99%

<p>Characterization and bioactivity of self-assembled anti-angiogenic chondroitin sulphate-ES2-AF nanoparticle conjugate</p>

Liang¹,

Sun²,

Wang³

et al. 2019

IJN

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Background In the past few years, significant progress has been made in inhibiting neovascularization at the tumor site, cutting off the nutrient supply of the tumor, and inhibiting tumor growth and metastasis. However, many proteins/peptides have the disadvantage of poor stability, short half-life, and uncertain targeting ability. Chemical modification can be used to overcome these disadvantages; many polyethylene glycol-modified proteins/peptides have been approved by US FDA. The purpose of this study was to obtain a novel anti-angiogenic chondroitin sulfate (CS)-peptide nanoparticle conjugate with efficient anti-neovascularization and tumor targeting ability and an acceptable half-life. Materials and methods The CS-ES2-AF nanoparticle conjugate was synthesized and characterized using 1 H-nuclear magnetic resonance spectroscopy, transmission electron microscopy, and particle size and zeta potential analyzer. The anti-angiogenic ability was studied using MTT, migration, tube formation, and chick chorioallantoic membrane assays. The targeting ability of CS-ES2-AF was studied by ELISA, surface plasmon resonance, and bioimaging. The pharmacokinetics was also studied. Results The CS-ES2-AF could self-assemble into stable nanoparticles in aqueous solution, which significantly enhances its anti-neovascularization activity, tumor targeting more explicit, and prolongs its half-life. Conclusion CS is an effective protein/peptide modifier, and CS-ES2-AF displayed good potential in tumor targeting therapy.

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Section: Introductionmentioning

confidence: 99%

<p>Characterization and bioactivity of self-assembled anti-angiogenic chondroitin sulphate-ES2-AF nanoparticle conjugate</p>

Liang¹,

Sun²,

Wang³

et al. 2019

IJN

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“…Nature imparts diversity in peptides and proteins by chemical modifications to confer additional functional and structural properties after their biosynthesis . Inspired by Nature's machinery, there have been tremendous efforts to develop synthetic methodologies that allow the structure and function of existing proteins to be reengineered, thereby providing new avenues for the innovation of biocatalysts, biomaterials and therapeutic research …”

Section: Introductionmentioning

confidence: 99%

“…[1,2] Inspired by Nature's machinery, there have been tremendous efforts to develop synthetic methodologies that allow the structure and function of existing proteins to be reengineered, thereby providing new avenues for the innovation of biocatalysts, [3] biomaterials [4] and therapeutic research. [5] Given the stringent demands for stability, biocompatibility and biosafety in modern applications, the formation of a homogeneous, well-defined bioconjugate is crucial. To achieve this, chemical modifications need to be introduced at a single, distinct site (regioselectivity/site-selectivity) in high yields under mild conditions, preferably with retained tertiary structure and function.…”

Section: Introductionmentioning

confidence: 99%

Site‐Selective Disulfide Modification of Proteins: Expanding Diversity beyond the Proteome

Kuan

Wang

Weil

2016

Chemistry A European J

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The synthetic transformation of polypeptides with molecular accuracy holds great promise for providing functional and structural diversity beyond the proteome. Consequently, the last decade has seen an exponential growth of site‐directed chemistry to install additional features into peptides and proteins even inside living cells. The disulfide rebridging strategy has emerged as a powerful tool for site‐selective modifications since most proteins contain disulfide bonds. In this Review, we present the chemical design, advantages and limitations of the disulfide rebridging reagents, while summarizing their relevance for synthetic customization of functional protein bioconjugates, as well as the resultant impact and advancement for biomedical applications.

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“…The chemical modification of proteins has been developed to a core discipline in chemical biology with diverse applications in all areas of the life sciences, including pharmacology, biophysics, biotechnology and cell biology [1–4]. In addition to the use of chemical labeling methods to study structure and function of proteins in vitro and in vivo, chemoselective conjugation techniques are also used to functionalize artificial protein scaffolds, such as viral capsids [5–7].…”

Section: Introductionmentioning

confidence: 99%

Orthogonal dual-modification of proteins for the engineering of multivalent protein scaffolds

Mühlberg

Hoesl

Kranjec

et al. 2015

Beilstein J. Org. Chem.

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SummaryTo add new tools to the repertoire of protein-based multivalent scaffold design, we have developed a novel dual-labeling strategy for proteins that combines residue-specific incorporation of unnatural amino acids with chemical oxidative aldehyde formation at the N-terminus of a protein. Our approach relies on the selective introduction of two different functional moieties in a protein by mutually orthogonal copper-catalyzed azide–alkyne cycloaddition (CuAAC) and oxime ligation. This method was applied to the conjugation of biotin and β-linked galactose residues to yield an enzymatically active thermophilic lipase, which revealed specific binding to Erythrina cristagalli lectin by SPR binding studies.

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More than add-on: chemoselective reactions for the synthesis of functional peptides and proteins

Cited by 87 publications

References 62 publications

<p>Characterization and bioactivity of self-assembled anti-angiogenic chondroitin sulphate-ES2-AF nanoparticle conjugate</p>

<p>Characterization and bioactivity of self-assembled anti-angiogenic chondroitin sulphate-ES2-AF nanoparticle conjugate</p>

Site‐Selective Disulfide Modification of Proteins: Expanding Diversity beyond the Proteome

Orthogonal dual-modification of proteins for the engineering of multivalent protein scaffolds

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