Psoralens

Psoralen is a compound derived from plants, naturally occurring as an insecticide, which becomes active when exposed to light. It increases the skin's sensitivity to longwave ultraviolet radiation, making it effective in UV light therapy. In this therapy, psoralen is absorbed into the epidermal cells where it interacts with human DNA under UV light. Psoralen has been utilized to treat skin conditions such as vitiligo, psoriasis, and specific types of skin nodules associated with cutaneous T-cell lymphoma. This compound is found in various plants including figs, celery, parsley, parsnip, clove, and citrus fruits, and can be administered topically or orally for medicinal purposes.

Psoralen belongs to the furocoumarin family and must be used with UV light therapy to achieve therapeutic effects. It intercalates with DNA and RNA, and upon exposure to UVA light at 365 nm, it causes cross-linking between DNA pyrimidine bases, disrupting replication and arresting the cell cycle. Click chemistry, discovered by Rolf Huisgen and named by Karl Barry Sharpless, facilitates the development of site-specific nucleic acid probes through bioconjugation, allowing for the creation of naturally characteristic products by joining molecular units.

Psoralen has diverse pharmacological effects. Used with UVA radiation (PUVA therapy), it treats psoriasis, vitiligo, and skin nodules linked to cutaneous T-cell lymphoma. It also has anti-viral and anti-inflammatory properties, enhances UVA light absorption, reduces skin inflammation, and shows potential in treating osteoporosis by increasing gene expression of osteoblast markers and boosting bone formation. Additionally, psoralen inhibits Mycobacterium tuberculosis H37Rv and Phytophthora cinnamomi mycelia, indicating possible applications as a pesticide.

Applications of Psoralen

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Psoralen finds various applications. Primarily, it is used with UVA radiation (PUVA therapy) to treat dermatological conditions like psoriasis and vitiligo. It is also effective in treating cancers such as cutaneous T-cell lymphoma by targeting rapidly dividing cells with its light-reactive properties. Psoralen's ability to promote bone formation and density makes it a potential treatment for osteoporosis.

AAT Bioquest offers several Psoralen conjugates, including those derived from trimethylpsoralen (TMP) and methoxypsoralen (MOP). Both are photosensitive and reactive to UV light, with some conjugates capable of biotinylating DNA or RNA. These conjugates are excellent for developing site-specific nucleic acid probes via the well-known click chemistry, specifically Copper-Catalyzed Azide-Alkyne Cycloaddition (CuAAC). Psoralens and their derivatives, like 8-MOP and 4,5',8-TMP, are recognized for their unique DNA crosslinking features. Although crosslinking is common, psoralen monomers lack sequence-specific crosslinking abilities with target DNA. Research by Nakao et al. indicates that 5-MOP is more effective at crosslinking DNA compared to 8-MOP. These conjugates can be used to prepare TMP- or MOP-labeled oligos from alkynyl- or azido-modified oligos.

Psoralen TMP Azide is an alkynyl-reactive TMP derivative that can be readily conjugated to azido-containing biomolecules (such as alkynyl-modified antibodies, peptide alkynes, and alkynyl-modified oligos).

Psoralen MOP Azide is an alkynyl-reactive 5-MOP derivative that can be readily conjugated to azido-containing biomolecules (such as alkynyl-modified antibodies, peptide alkynes, and alkynyl-modified oligos).

Psoralen TMP Alkyne is an azide-reactive TMP derivative that can be readily conjugated to azido-containing biomolecules (such as azido-modified antibodies, peptide azides, and azido-modified oligos).

Psoralen MOP Alkyne is an azide-reactive 5-MOP derivative that can be readily conjugated to azido-containing biomolecules (such as azido-modified antibodies, peptide azides, and azido-modified oligos).

AAT Bioquest also provides Psoralen TMP Maleimide, a thiol-reactive TMP derivative. The TMP-conjugated oligonucleotide can be used for sequence-specific crosslinking with a target DNA, thus enabling the application of psoralen-conjugated molecules in gene transcription inhibition, gene knockout, and other genomic applications. Psoralen TMP Maleimide may also be used for preparing site-specific DNA/RNA probes via the conjugations with thiol-containing biomolecules such as antibodies.

Psoralen MOP Maleimide is a 5-MOP derivative offered by AAT Bioquest, where the 5-MOP-conjugated oligonucleotides can be used for sequence-specific crosslinking with a target DNA, thus enabling the application of psoralen-conjugated molecules in gene transcription inhibition, gene knockout, and other genomic applications.Psoralen TMP Maleimide is also useful for preparing site-specific DNA/RNA probes through conjugation with thiol-containing biomolecules such as antibodies.

An additional Psoralen conjugate offered by AAT Bioquest is Psoralen TMP Succinimidyl Ester. Contrary to the TMP Maleimides, TMP Succinimidyl Ester is an amino-reactive TMP derivative.

Psoralen MOP Succinimidyl Ester, another ester conjugate, is available from AAT Bioquest for purchase.

Both Psoralen TMP Succinimidyl Ester and Psoralen MOP Succinimidyl Ester may be used for preparing site-specific DNA/RNA probes via the conjugations with amino-containing biomolecules such as antibodies.

Psoralen-PEG3-Biotin is available as a photoactivable reagent for biotinylating DNA or RNA, which can intercalate into double-stranded DNA or RNA and form covalent bonds with thymine and other pyrimidine bases when exposed to UV light (around 350 nm). With a polyethylene glycol (PEG) spacer arm (~45 Å), it enhances the solubility and accessibility of the biotin moiety. Psoralen-PEG3-Biotin is used for selective labeling of cell surface proteins, biotinylation of hyaluronan, labeling of endotoxin for receptor binding studies, and crosslinking of nucleic acids for genomic investigations. It is also valuable for studying nucleic acid and protein interactions.

ReadiLink™ Psoralen-A17-Biotin is also offered as a photoactivable reagent for biotinylating DNA or RNA. Compared to Psoralen-PEG3-Biotin, Psoralen-A17-Biotin is more effective under the same conditions and is a superior alternative. Psoralen-A17-Biotin can be used for selective labeling of cell surface proteins, tissues, and other biological samples. It can also be used to study the interactions between nucleic acids and proteins.

Resources

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Introduction: Click Chemistry
What Is Psoralen?
Unique Crosslinking Properties of Psoralen-Conjugated Oligonucleotides Developed by Novel Psoralen N-Hydroxysuccinimide Esters