saporin

He X, Qu Y, Xiong S, Jiang Z, Tang Y, Yan F, Deng Y, Sun Y (2023) Functional l-arginine derivative as an efficient vector for intracellular protein delivery for potential cancer therapy. J Funct Biomater 14(6):301. doi: 10.3390/jfb14060301 PMID: 37367265

Objective: To address the instability of the 9-fluorenylmethyloxycarbonyl (Fmoc) group in aqueous medium.

Summary: The Fmoc ligand neighboring arginine was substituted for dibenzocyclooctyne (DBCO) with a similar structure to Fmoc to obtain stable DBCO-functionalized L-arginine derivative (DR). DBCO-functionalized L-arginine derivative represents an excellent potential vector for protein-based cancer therapy.

Usage: The synthesized DR monomer was first dissolved in sterilized ultrapure water with a concentration of 1 mg/mL, then mixed with protein solution at a weight ratio of 5:1 for saporin (DR:SA) for 10 min at room temperature. Saporin was added at 110μg/mL to MDA-MB-231 cells (DR: SA-FITC: HA,w:w:w, 5:1:25)

Related Products: Saporin (Cat. #PR-01)

Porello I, Cellesi F (2023) Intracellular delivery of therapeutic proteins. New advancements and future directions. Front Bioeng Biotechnol 11:1211798. doi: 10.3389/fbioe.2023.1211798 PMID: 37304137

Objective: To provide a brief overview of the current methods for intracellular protein delivery to mammalian cells.

Summary: The field of intracellular protein delivery is still a relatively young area of research and further advancements in this field will require the integration of chemistry, materials science, formulation science, nanomedicine, and biomedical engineering.

Usage: Saporin was referenced as a molecule with the advantage of being able to block the synthesis of proteins in cells.

Related Products: Saporin (Cat. #PR-01)

Holborough-Kerkvliet MD, Kroos S, van de Wetering R, Toes REM (2023) Addressing the key issue: Antigen-specific targeting of B cells in autoimmune diseases. Immunol Lett 259:37-45. doi: 10.1016/j.imlet.2023.05.005 PMID: 37209914

Objective: Using cyclic citrullinated peptide (CCP) conjugated to CNBz and saporin to eliminate autoreactive B cells, as a treatment for rheumatoid arthritis (RA).

Summary: Joint damage in the body creates cyclic citrullinated peptide (CCP) which is a marker of Rheumatoid arthritis (RA). The CCP active site that autoantibodies target is blocked with CNBz and the whole complex is conjugated with saporin allowing cytotoxicity directed towards autoreactive B cells, a damaging element of RA, without being reactive with CCP-targeted autoantibodies.

Related Products: Saporin (Cat. #PR-01)

See Also:

• Lelieveldt LPWM et al. Sequential prodrug strategy to target and eliminate ACPA-selective autoreactive B cells. Mol Pharm 15(12):5565-5573, 2018.

Chen LQ, Lv XJ, Guo QH, Lv SS, Lv N, Xu WD, Yu J, Zhang YQ (2023) Asymmetric activation of microglia in the hippocampus drives anxiodepressive consequences of trigeminal neuralgia in rodents. Br J Pharmacol 180(8):1090-1113. doi: 10.1111/bph.15994 PMID: 36443951

Objective: To determine whether and how microglia are involved in trigeminal neuralgia-induced anxiodepression.

Summary: Findings suggest that priming of microglia with ATP/P2X7 receptors in the ipsilateral hippocampus drives pain-related anxiodepressive-like behaviors via IL-1β. An asymmetric role of the bilateral hippocampus in trigeminal neuralgia-induced anxiety and depression was uncovered.

Usage: Mac-1–SAP (IT-06, 2.5 μg/1 μl, per side) was bilaterally injected into the hippocampal CA1 area on Day 0 and Day 7 after constriction of the infraorbital nerve, respectively. Unconjugated saporin was used as a control.

Related Products: Saporin (Cat. #PR-01), Mac-1-SAP mouse/human (Cat. #IT-06)

Singh SA, Vellapandian C (2023) The promising guide to LC–MS analysis and cholinesterase activity of Luffa cylindrica (L.) fruit using in vitro and in-silico analyses. Futur J Pharm Sci 9:33. doi: 10.1186/s43094-023-00478-0

Objective: Identify and analyze the extract of the plant Luffa cylindrica for bioactive and biochemical properties, particularly as it relates to bioactivity in neurological diseases.

Summary: Luffa cylindrica contains a total of 80 compounds that were identified in the ethanolic extract from LC–MS analysis. The bioactive compounds were screened for activity in receptors responsible for causing oxidative stress-associated Alzheimer’s disease. Perlolyrine was chosen to perform in-silico docking. An in vitro activity of cholinesterase showed highest inhibition at 500 μg/ml. In-silico docking of perlolyrine showed better binding affinity and score. Results revealed that out of 10 docked receptors, amyloid beta showed the highest binding affinity with an energy of −46.1 kcal/mol showing promising drug for Alzheimer’s disease. The study reports the presence of a promising, bioactive compound (perlolyrine) with promisng applications in vivo, oxidative stress-related Alzheimer’s disease.

Related Products: Saporin (Cat. #PR-01)

See Also:

• Santosh et al (2015) Mechanism of Anti-HIV Activity of Ribosome Inactivating Protein, Saporin. Protein & Peptide Letters. 22(6): 497-503. doi: 10.2174/0929866522666150428120701

Son H, Shin J, Park J (2023) Recent progress in nanomedicine-mediated cytosolic delivery. RSC Adv 13(15):9788-9799. doi: 10.1039/D2RA07111H PMID: 36998521

Summary: Cytosolic delivery of drugs, like saporin, through nanocapsules offers ways to move proteins through the body with greater specificity and efficacy. A nanoparticle that released a modified saporin protein at pH conditions correlative conditions to a tumor micro-environment was discussed as a model to deliver peptide-drugs to the cytosol.

Mohammad Hadi L, Stamati K, Yaghini E, MacRobert AJ, Loizidou M (2023) Treatment of 3D in vitro tumoroids of ovarian cancer using photochemical internalisation as a drug delivery method. Biomedicines 11(2):572. doi: 10.3390/biomedicines11020572 PMID: 36831108

Objective: To examine the efficacy of Photochemical internalization (PCI) using a porphyrin photosensitiser and a cytotoxin (Saporin) on ovarian cancer tumouroids, with HEY ovarian cancer cells in the central cancer compartment, and HDF fibroblast cells and HUVEC endothelial cells in the surrounding stromal compartment.

Summary: The efficacy was compared to tumouroids treated with either Saporin or PDT alone, or no treatment. PCI treatment was shown to be effective in the tumouroids (determined through viability assays and imaging) and caused a considerable decrease in the viability of cancer cells both within the central cancer mass and those which had migrated into the stroma, as well as a reduction in the cell density of surrounding HUVEC and HDF.

Usage: Saporin (PR-01, 20 nM) was carried out on complex tumouroids.

Related Products: Saporin (Cat. #PR-01)

Hankerd K, Koo H, McDonough KE, Wang J, Pariyar R, Tang SJ, Chung JM, La JH (2023) Gonadal hormone-dependent nociceptor sensitization maintains nociplastic pain state in female mice. Pain 164(2):402-412. doi: 10.1097/j.pain.0000000000002715 PMID: 35975896

Objective: To determine whether gonadal hormones are necessary for the development and maintenance of a peripherally maintained nociplastic pain state in female mice.

Summary: Ovariectomized females still developed a nociplastic pain state, but it was not maintained by peripheral afferent activity or spinal microglia. The findings indicate that gonadal hormones are essential for sustaining this pain state by promoting persistent sensitization of AITC-responsive afferents.

Usage: Mac-1-SAP (IT-06) or unconjugated saporin (PR-01) was administered intrathecally at 8.85 µM in 5 µL to evaluate the role of spinal microglia in nociplastic pain maintenance.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)

Q: I read on your website that, “There are two types of RIPs: type I, which are much less cytotoxic due to the lack of the B chain and type II, which are distinguished from type I RIPs by the presence of the B chain and their ability to enter cells on their own.”

In the IT-27 Streptavidin-ZAP product, which type of saporin is there? Is it both type I and type II because the saporin is purified from the plant, or is it one specific type only in the product.

A: All saporin molecules are Type I ribosome-inactivating proteins. We only use saporin. An example of a Type II RIP is ricin, which can enter a cell on its own and has been used throughout history as a method of assassination.

Streptavidin-ZAP is streptavidin attached to saporin. On its own it has no way to get inside a cell. By mixing Streptavidin-ZAP with a biotinylated molecule that is recognized on the cell surface, the resulting conjugate is able to bind and internalize saporin into a cell. Once inside saporin inactivates the ribosomes which causes cell death.

Yamaguchi S, Yamamoto K, Yamamoto R, Takamori S, Ishiwatari A, Minamihata K, Nagamune T, Okamoto A (2022) Intracellular protein photoactivation using sterically bulky caging. Chembiochem 23(22):e202200476. doi: 10.1002/cbic.202200476 PMID: 36173993

Objective: To develop an intracellular protein photoactivation method using sterically bulky caging.

Summary: Saporin was biotinylated and conjugated to streptavidin to block the active site of saporin. This temporarily inactivated protein was then activated via the cleaving of the streptavidin linker through light. This simple and versatile photoactivation method is a promising tool for studying spatio-temporal cellular events.

Usage: A sterically bulky caged Sap (cSap) was prepared via the two-step caging method using a biotinylated caging reagent (BCR). In the first step, Saporin (PR-01) was randomly modified with BCR via the amide coupling reaction. In the second step, streptavidin was conjugated with the biotin moiety on the BCR-modified Sap.

Related Products: Saporin (Cat. #PR-01)