Prolonging the Action of Protein and Peptide Drugs by a Novel Approach of Reversible Polyethylene Glycol Modification

Tsubery, Haim; Mironchik, Marina; Fridkin, Mati; Shechter, Yoram

doi:10.1074/jbc.m405155200

Cited by 71 publications

(53 citation statements)

References 26 publications

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“…14,16 Although, several alternate pegylation strategies exist, it seems that irrespective of the approach, the derivatized protein polymer requires a number of purification steps and gives low yields, thus making the process expensive and cost ineffective. 13,17,18 An advancement in this field was made by expressing human IFNa2b (IFNa2b/IFNa2) as an arabinogalactanprotein (AGP) fusion in tobacco cells. 13 This approach involves specific hydroxyproline-O-glycosylation, a posttranslational modification unique to plants and green algae.…”

mentioning

confidence: 99%

Novel Fusion Proteins of Interferon α2b Cause Growth Inhibition and Induce JAK-STAT Signaling in Melanoma

Fernandes¹,

Soans²,

et al. 2010

Journal of Immunotherapy

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Melanoma is an aggressive form of skin cancer with high occurrence in the United States. Interferon alpha2b (IFNalpha2b/IFNalpha2) has been used in high doses to treat melanoma. However, problems associated with small molecule therapeutics such as with IFN treatment include small molecular size, degradation by serum proteases, and rapid kidney clearance. Pegylation has been used to overcome this, but in itself possesses a host of other issues such as decrease receptor binding, nonspecific chemical derivatization, low overall yields, and additional purification steps. An alternative to this produces IFN as arabinogalactan fusion proteins in plant cells. These IFN analogs bind to IFN receptors and follow the IFN-induced Janus Kinase 1-signal transducers and activators of transcription signaling pathway. Here, we show that these fusion proteins of higher molecular weight also cause similar growth inhibition and affect cell cycle distribution in melanoma cells M92-047 and SK MEL-28. Lastly, the fusion proteins increased translation of 2'5'-oligo adenylate synthetase and Protein Kinase R, known IFN-induced proteins, showing similar downstream signaling as native recombinant IFNalpha2.

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mentioning

confidence: 99%

Novel Fusion Proteins of Interferon α2b Cause Growth Inhibition and Induce JAK-STAT Signaling in Melanoma

Fernandes¹,

Soans²,

et al. 2010

Journal of Immunotherapy

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“…In both strategies the linkers comprise an ester bond; after hydrolysis it releases the drug-linker moiety, which in turn undergoes a rearrangement yielding the free drug or protein [55,56]. • 2-sulfo-9-fluorenylmethoxycarbonyl linker [57];…”

Section: Figurementioning

confidence: 99%

Drug and protein delivery by polymer conjugation

Grigoletto

Maso

Mero

et al. 2016

Journal of Drug Delivery Science and Technology

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“…The reaction of 11 with 3-maleimidopropionic acid 45 followed by Boc deprotection and diazotation was unsuccessful and did not improve significantly when using the more reactive acetyl chloride 46 or anhydride 47 derivatives of 3-maleimidopropionic acid. Solid-phase synthesis (SPS) methodology 48 with 2-chlorotrityl chloride resin 49 in a vessel gave the desired product (Scheme 4).…”

Section: Benzophenone Probes and Their Application To Glycoside Substmentioning

confidence: 99%

Development of bifunctional photoactivatable benzophenone probes and their application to glycoside substrates

Qvit¹,

Monderer-Rothkoff²,

Ido³

et al. 2008

Biopolymers

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Photoaffinity labeling is used to covalently attach ligands to macromolecules to determine their spatial arrangement and structure. Benzophenone (BP) groups are widely used for covalent photoaffinity labeling and for probing protein interactions. We developed bifunctional BP photoactivatable derivatives using three different general chemical approaches. In addition to the photoaffinity reactivity of the BP, these derivatives contain an additional group: A radioactive tracer for biological studies, or an N-ethylmaleimide group as an additional crosslinker, or a biotin group to be used during purification and characterization of probe-protein complexes using the high-affinity biotin-avidin interaction. A model series of photoaffinity labeling probes was synthesized based on the arbutin ligand. These compounds can be used as probes to study the arbutin binding site of microbial beta-glucoside transporters by photolabeling residues in its vicinity. The second functionality provides additional options for studying proteins and binding sites. The probes were developed using different methodologies: (i) a diazotation reaction; (ii) protecting group methodology; and (iii) solid-phase synthesis. These procedures are general and provide a simple and versatile approach for synthesizing bifunctional BP ligands, as demonstrated here on arbutin.

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Prolonging the Action of Protein and Peptide Drugs by a Novel Approach of Reversible Polyethylene Glycol Modification

Cited by 71 publications

References 26 publications

Novel Fusion Proteins of Interferon α2b Cause Growth Inhibition and Induce JAK-STAT Signaling in Melanoma

Novel Fusion Proteins of Interferon α2b Cause Growth Inhibition and Induce JAK-STAT Signaling in Melanoma

Drug and protein delivery by polymer conjugation

Development of bifunctional photoactivatable benzophenone probes and their application to glycoside substrates

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