Avtor/Urednik		Maraković, Nikola; Šinko, Goran
Naslov		The lock is the key
Tip		članek
Vol. in št.		Letnik 64, št. 1
Leto izdaje		2017
Obseg		str. 15-39
ISSN		1318-0207 - Acta Chimica Slovenica
Jezik		eng
Abstrakt		Modern drug discovery is mainly based on the de novo synthesis of a large number of compounds with a diversity of chemical functionalities. Though the introduction of combinatorial chemistry enabled the preparation of large libraries of compounds from so-called building blocks, the problem of successfully identifying leads remains. The introduction of a dynamic combinatorial chemistry method served as a step forward due to the involvement of biological macromolecular targets (receptors) in the synthesis of high affinity products. The major breakthrough was a synthetic method in which building blocks are irreversibly combined due to the presence of a receptor. Here we present various receptor-based combinatorial chemistry approaches. Huisgen's cycloaddition (1,3-dipolar cycloaddition of azides and alkynes) forms stabile 1,2,3-triazoles with very high receptor affinity that can reach femtomolar levels, as the case with acetylcholinesterase inhibitors shows. Huisgen's cycloaddition can be applied to various receptors including acetylcholinesterase, acetylcholine binding protein, carbonic anhydrase-II, serine/threonine-protein kinase and minor groove of DNA.
Proste vsebinske oznake		načrtovanje zdravil dinamična kombinatorna kemija Huisgenova cikloadicija drug design dynamic combinatorial chemistry Huisgen's cycloaddition