A chemically stabilized DNA barcode for DNA-encoded libraries

Sehr geehrte Kolleginnen und Kollegen, wir laden herzlich zu einer Vortragsveranstaltung am Dienstag, den 25.10.2022, um 18 Uhr c.t. per ZOOM oder in den großen Hörsaal der Pharmazeutischen Institute, Corrensstraße 48 in Münster ein.

Zoom-Link
Meeting ID: 662 2161 3926
Passcode: DPhG

DNA-encoded libraries are investigated by many pharmaceutical companies and academic research groups as small molecule screening technology. The design of these libraries is a generative chemistry problem. Validated DEL designs rely on the narrow canon of heavily utilized parallel synthesis reaction methods. These use carbonyl chemistry, cross-coupling reactions, and only a very few heterocycleforming reactions. Thus, validated library design is focused on a small area of the vast chemical reaction space. This area of reaction space furnishes primarily unsaturated, flat-shaped products. We developed a barcoding strategy based on chemically stabilized DNA barcodes that allows, in principle, to use amuch larger reaction spectrum. The reasons for this are a greater chemical stability to protic acids, andan optional solid phase-initiated DEL synthesis strategy that prevents barcode nucleobase deaminationand allows for dry conditions in encoded compound synthesis. Arguably, the transition from barcoding methods development to parallelization and scaling for library synthesis is challenging. Non-standard reactions for DEL design and their scope will be discussed. They include a suite of heterocyclic scaffold forming reactions, including isocyanide multi-component reaction chemistries. Pooling strategies for encoded substrates are developed to provide high-quality pools for further DEL built. Beyond current DEL synthesis, a computational workflow for the identification of suitable DEL reactions from large chemistry databases will be shown, the assessment of reactions fit for purpose and our approach to reaction translation.

Ich würde mich freuen, Sie zusammen mit Ihren Mitarbeitern begrüßen zu können.

Mit freundlichen Grüßen
Anna Junker