{"id":1298,"date":"2021-04-21T12:15:30","date_gmt":"2021-04-21T16:15:30","guid":{"rendered":"https:\/\/neoaptamers.com\/?p=1298"},"modified":"2026-04-14T10:10:56","modified_gmt":"2026-04-14T14:10:56","slug":"frelex","status":"publish","type":"post","link":"https:\/\/neoaptamers.com\/es\/frelex\/","title":{"rendered":"FRELEX: \u201cThe concept\u201d"},"content":{"rendered":"
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In the M.C. Escher painting, \u201cReptiles\u201d it is clear how much more information is present in the three-dimensional representation of the lizards versus their two-dimensional counterparts. The three-dimensional lizards are alive, they are bending over and interacting with surfaces. I will argue that the situation is similar with the\u00a0\u00a0 development of antibodies or aptamers for small molecules. There is information that is being lost in the way we select these ligands.<\/p>

Antibodies do not recognize small molecules in their free state, this is referred to as a lack of sufficient antigenicity. The small molecule must be conjugated to a larger molecule in order to enable antibody selection. The same is true with traditional SELEX aptamer selection as the target molecule needed to be immobilized in order to enable the partitioning of bound aptamers from unbound ones. This tethering of the small molecule to a surface decreases the information present in the small molecule. With molecules this loss of information is manifested in the removal of charge groups that could enter into Van der Waals forces or hydrogen bond interactions with nucleotides in aptamers. The conjugation also has the potential to change the distance between atoms and the resonance of forces within the molecule. Bottom line, conjugating a small molecule to a larger ones diminishes what is interesting in the small molecule, it decreases the target molecules ability to interact with an aptamer.<\/p>

At NeoVentures we have developed a patented approach to selecting aptamers for small molecules in their free state that we have called FRELEX. The basis of the approach is the potential for all aptamers to hybridize to random 8mers that are immobilized on a surface. We combine aptamers with a free target and expose this mixture to a surface coated with random 8mers. Aptamers that bind to the free target are less likely to hybridize to the 8mers than aptamers that do not bind to the free target. This really is a negative selection in that we select aptamers that bind to the free small molecule target by capturing those that are not bound to the immobilized 8mers.<\/p>

FRELEX is used in a manner similar to SELEX. We retain the aptamers that are bound to the free target, PCR amplify them and repeat the selection process. We increase the stringency of selection by repeating the selection process more times within each selection round prior to PCR amplification. Counter selection is introduced by combining the aptamer library with the counter selection target and retaining those sequences that hybridize to the immobilized random 8mers. With this approach we have succeeded in identifying aptamers for molecules less than 1000 daltons in molecular weight.<\/p>

The binding affinity of a small molecule to any ligand, antibody or aptamer is more a function of the binding capacity of the small molecule than it is of the ligand. By maintaining the presence of all of the information in the small molecule, especially all of the charge groups we increase the potential binding affinity between the selected aptamers and these targets. In a future blog we will discuss more applications of this breakthrough platform.<\/p>

FRELEX succeeds by maintaining the full reality of the target molecules. By allowing the reptiles to escape from his canvas Escher achieves the same effect. The three-dimensional forms of the creatures are alive, more capable of interacting with their environment. With FRELEX we are able to release small molecules from conjugation and allow them to express themselves in their full real world form. This allows us to develop aptamers that bind to the beautiful, real-world form of each molecule.<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<\/div>","protected":false},"excerpt":{"rendered":"

In the M.C. Escher painting, \u201cReptiles\u201d it is clear how much more information is present in the three-dimensional representation of the lizards versus their two-dimensional counterparts. The three-dimensional lizards are alive, they are bending over and interacting with surfaces. I will argue that the situation is similar with the\u00a0\u00a0 development of antibodies or aptamers for… Leer m\u00e1s »FRELEX: \u201cThe concept\u201d<\/span><\/a><\/p>","protected":false},"author":1,"featured_media":1303,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"neve_meta_sidebar":"","neve_meta_container":"","neve_meta_enable_content_width":"off","neve_meta_content_width":70,"neve_meta_title_alignment":"","neve_meta_author_avatar":"","neve_post_elements_order":"","neve_meta_disable_header":"","neve_meta_disable_footer":"","neve_meta_disable_title":"","footnotes":""},"categories":[8,7],"tags":[],"class_list":["post-1298","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-aptamers","category-frelex"],"yoast_head":"\nFRELEX: \u201cThe concept\u201d<\/title>\n<meta name=\"description\" content=\"We have developed a patented approach to selecting aptamers for small molecules in 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