A needle in a haystack
The search for new medicines is like fishing: it requires patience, skill and material investments, and the prospect of catching something worthwhile is very vague. Researchers from the Swiss Higher Technical School of Zurich (Eidgenössische Technische Hochschule, ETH), led by Dario Neri, have developed a new method that will accelerate the development of new drugs, make it cheaper and more effective.
The method is based on a library of DNA-encoded chemical compounds (DNA-encoded chemical library, DECL), which contains 35 million different potential drugs.
Each substance from this library can be a medicine, it has a stable structure in the form of rings. Chemists attached three different molecules to these rings. As a result, a structure resembling a fish hook that can "pick up" a protein strictly corresponding to it.
The researchers combined hundreds of such molecules, creating a DECL library of 35 million "hooks" as a result.
The scheme of three molecules was encoded in three short DNA sequences, which, like a barcode, will help scientists quickly identify each "hook".
A drawing from an article in Nature Chemistry.
The authors tested a system for quickly selecting the necessary substance from 35 million compounds. In order to determine which "hook" is needed, they placed the entire DECL library in a solution containing a specific protein. After a while, all the compounds from the library that did not bind to the protein were washed, and the remaining ones were easily identified using DNA code. Thus, the entire collection was checked for matches in just one go.
DECL technology is inexpensive, efficient and easy to use. If you "hang" a cytotoxic molecule on a hook compound, you can try using DECL to fight cancer: the hook, picking up a target protein characteristic of a tumor cell, would release a toxin that is harmful to it.
A similar strategy, but using an antigen-antibody complex, has been tested before. But the relatively large size of the proteins did not allow them to penetrate deep into the tumor. The authors hope that molecular hooks from the DECL library will be able to implement this method of cancer treatment.
Article by Y. Li et al. Versatile protein recognition by the encoded display of multiple chemical elements on a constant macrocyclic scaffold is published in the journal Nature Chemistry.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on EurekAlert: Catching the right fish.