You are cordially invited to attend the seminar organized by the Department of Chemistry.<\/p>\n
Title: Drug-like ligands for DC-SIGN receptor
\nSpeaker: Dr. Petra M\u00e9nov\u00e1
\nDepartment of Organic Chemistry, University of Chemistry and Technology,
\nPrague, Czech Republic<\/p>\n
Date: March 30, 2023, Thursday
\nTime: 12:30 (Bilkent time), 11:30 CET<\/p>\n
This is an online seminar. To request the event link, please send a message to department.<\/p>\n
Abstract:
\nLectins are carbohydrate-binding proteins that play important roles in
\ncell-cell recognition, cell migration and immunitv. Their targeting is
\nchallenging because of inherent properties of their natural substrates
\ncarbohydrates: high polarity, low enzymatic stability, low affinity and
\nability to bind to numerous targets. While nature overcomes these
\nproblems with multivalency and exploits the recognition of oligo and
\npolysaccharides, medicinal chemists glycomimetics \u2013 synthetic structures
\nthat may or may not contain a carbohydrate-based core and lipophilic
\nfragments that interact with non-polar regions of the protein.<\/p>\n
DC-SIGN is a lectin receptor expressed on the surface of dendritic cells
\nand macrophages. It recognized mannose- and fucose-containing
\ncarbohvdrates in the alvcocalvx of numerous pathogens and mediates their
\nrecognition and elimination. As for other lectins, its carbohydrate
\nbinding site is shallow and hydrophilic and does not interact well with
\ndrug-like molecules<\/p>\n
We employ the principles of fragment-based drug discovery to identify
\nsecondary binding sites on DC-SIGN and develop new ligands for this
\ninteresting target. Several non-carbohydrate scaffolds have been
\nidentified and evaluated in structure-activity relationship studies. An
\napproach called fraament linking led to several hits with improved
\nbinding affinity and allosteric activity. Carbohydrate-based
\nglycomimetics showed interesting properties when interacting with
\nsecondary binding sites rather that the carbohydrate binding site.<\/p>\n
In my lecture, I will explain the principles of fragment-based drug
\ndiscovery and show some prominent examples from this field. Then I will
\nintroduce DC-SIGN as a target and show the results of fragment
\nscreening. I will talk about the synthesis of different classes of
\nglycomimetic DC-SIGN ligands and describe several biophysical methods
\nthat are used to evaluate their binding. Finally, I will show several
\npossible applications of the described compounds.<\/p>\n","protected":false},"excerpt":{"rendered":"
You are cordially invited to attend the seminar organized by the Department of Chemistry. Title: Drug-like ligands for DC-SIGN receptor Speaker: Dr. Petra M\u00e9nov\u00e1 Department of Organic Chemistry, University of Chemistry and Technology, Prague, Czech Republic Date: March 30, 2023, Thursday Time: 12:30 (Bilkent time), 11:30 CET This is an [\u2026] <\/p>\n