Modular synthesis of photocleavable peptides using click chemistry

Baccile, Joshua A.; Morrell, Mark A.; Falotico, Ross M.; Milliken, Brandon T.; Drew, Daniel L.; Rossi, Francis M.

doi:10.1016/j.tetlet.2012.02.002

Cited by 8 publications

(5 citation statements)

References 38 publications

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“…Further, as with the dfTAT model, the use of thiol coupling should provide stability and protect the cargo/CPP during systemic delivery. Another approach described by the Rossi lab utilizes an interesting photocleavable linkage to deliver cleaved peptides to the cytosol (48). While this may overcome entrapment, this strategy is seemingly impractical for many applications as it would be difficult to get light to many places within patients.…”

Section: Busting Out: Escape From the Endosomementioning

confidence: 99%

Breaking in and busting out: cell-penetrating peptides and the endosomal escape problem

LeCher

Nowak

McMurry

2017

Biomolecular Concepts

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Cell-penetrating peptides (CPPs) have long held great promise for the manipulation of living cells for therapeutic and research purposes. They allow a wide array of biomolecules from large, oligomeric proteins to nucleic acids and small molecules to rapidly and efficiently traverse cytoplasmic membranes. With few exceptions, if a molecule can be associated with a CPP, it can be delivered into a cell. However, a growing realization in the field is that CPP-cargo fusions largely remain trapped in endosomes and are eventually targeted for degradation or recycling rather than released into the cytoplasm or trafficked to a desired subcellular destination. This ‘endosomal escape problem’ has confounded efforts to develop CPP-based delivery methods for drugs, enzymes, plasmids, etc. This conceptual overview provides a brief history of CPP research and discusses current issues in the field with a primary focus on the endosomal escape problem, of which several promising potential solutions have been developed. Are we on the verge of developing technologies to deliver therapeutics such as siRNA, CRISPR/Cas complexes and others that are currently failing because of an inability to get into cells, or are we just chasing after another promising but unworkable technology? We make the case for optimism.

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Section: Busting Out: Escape From the Endosomementioning

confidence: 99%

Breaking in and busting out: cell-penetrating peptides and the endosomal escape problem

LeCher

Nowak

McMurry

2017

Biomolecular Concepts

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Section: Methodsmentioning

confidence: 99%

“…The design of the PCL was derived from 1‐(2‐nitrophenyl)propargyl alcohol, which was used as a photolytically cleavable linker of two peptide fragments . Nitrobenzene derivatives are appropriate linkers based on their photochemical properties and use as peptide caging groups . In order to avoid interference of deprotection with the nucleobase absorption, the wavelength for uncaging was shifted to λ =347 nm by applying the 3,4‐methoxy nitrobenzene derivative .…”

Section: Methodsmentioning

confidence: 99%

Native Chemical Ligation Directed by Photocleavable Peptide Nucleic Acid (PNA) Templates

et al. 2017

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A novel peptide-peptide ligation strategy is introduced that has the potential to provide peptide libraries of linearly or branched coupled fragments and will be suited to introduce simultaneous protein modifications at different ligation sites. Ligation is assisted by templating peptide nucleic acid (PNA) strands, and therefore, ligation specificity is solely encoded by the PNA sequence. PNA templating, in general, allows for various kinds of covalent ligation reactions. As a proof of principle, a native chemical ligation strategy was elaborated. This PNA-templated ligation includes easy on-resin procedures to couple linkers and PNA to the respective peptides, and a traceless photocleavage of the linker/PNA oligomer after the ligation step. A 4,5-dimethoxy-2-nitrobenzaldehyde-based linker that allowed the photocleavable linkage of two bio-oligomers was developed.

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“…23 An oNb-based substrate containing a tert-butyloxycarbonyl (Boc) protected amino-OEG 3 chain (oNb-OEG 3 ) was synthesised by adapting a method of Rossi and co-workers (Scheme 1). 24 Incorporation of an alkyne functional group at the benzylic position of the oNb derivative via a Grignard reaction gave 1. 17 Copper(I)-catalyzed azide-alkyne cyclo-addition (CuAAC) between 1 and 2 gave 3 in a yield of 72%, that was then reacted with paranitrophenyl chloroformate to produce 4 in 45% yield.…”

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confidence: 99%

The efficient synthesis and purification of amyloid-β(1–42) using an oligoethylene glycol-containing photocleavable lysine tag

et al. 2017

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A short, monodisperse oligoethylene glycol-containing photocleavable lysine tag was developed to facilitate the efficient purification of hydrophobic and fibril-forming peptides. This new tag was used to prepare a modified Aβ peptide with increased solubility and decreased propensity to aggregate in aqueous media. The solubilising tag was readily removed by irradiation with UV light and permitted the preparation and isolation of Aβ in high purity and yield.

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Modular synthesis of photocleavable peptides using click chemistry

Cited by 8 publications

References 38 publications

Breaking in and busting out: cell-penetrating peptides and the endosomal escape problem

Breaking in and busting out: cell-penetrating peptides and the endosomal escape problem

Native Chemical Ligation Directed by Photocleavable Peptide Nucleic Acid (PNA) Templates

The efficient synthesis and purification of amyloid-β(1–42) using an oligoethylene glycol-containing photocleavable lysine tag

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