Abstract
Saporin is a ribosome-inactivating protein that can cause inhibition of protein synthesis and causes cell death when delivered inside a cell. Development of commercial Saporin results in a technology termed ‘molecular surgery’, with Saporin as the scalpel. Its low toxicity (it has no efficient method of cell entry) and sturdy structure make Saporin a safe and simple molecule for many purposes. The most popular applications use experimental molecules that deliver Saporin via an add-on targeting molecule. These add-ons come in several forms: peptides, protein ligands, antibodies, even DNA fragments that mimic cell-binding ligands. Cells that do not express the targeted cell surface marker will not be affected. This review will highlight some newer efforts and discuss significant and unexpected impacts on science that molecular surgery has yielded over the last almost four decades. There are remarkable changes in fields such as the Neurosciences with models for Alzheimer’s Disease and epilepsy, and game-changing effects in the study of pain and itch. Many other uses are also discussed to record the wide-reaching impact of Saporin in research and drug development.
Highlights
Ribosome-inactivating proteins (RIPs) have long been thought of as potentially perfect payloads for the treatment of human tumors; they could be tools to make Ehrlich’s Magic Bullet to remove harmful cells without harming healthy ones [1]
A common property shared among RIPs is their highly specific RNA N-glycosidase activity that cleaves the glycosidic bond of a single adenine base (A4324 in rat) from the ribosomal RNA of the large subunit 28 s [2]
One of the things that is reliable with Saporin is that if it is part of a complex that binds to a cell surface target, it will be internalized
Summary
Ribosome-inactivating proteins (RIPs) have long been thought of as potentially perfect payloads for the treatment of human tumors; they could be tools to make Ehrlich’s Magic Bullet to remove harmful cells without harming healthy ones [1]. RIPs are very potent, often active in the picomolar range They can be targeted, as their corresponding bacterial toxins are, by attachment to molecules that bind to the cell surface and cause internalization. One of the things that is reliable with Saporin is that if it is part of a complex that binds to a cell surface target, it will be internalized This is not always the case with some of the toxin enzymatic chains. With Pseudomonas exotoxin, quite a bit of work went into the addition of sequence pieces outside of the enzymatic chain that were necessary for causing internalization and cell death [9–13] This was accomplished primarily by the group of Ira Pastan over many years and the result is an anti-tumor drug, Lumoxiti. Its related brother gelonin, are able to enter the cell along with its targeting agent with no extra additions to their sequences
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