Fragment Screening and Fast Micromolar Detection on a Benchtop NMR Spectrometer Boosted by Photoinduced Hyperpolarization

Author:

Stadler Gabriela R.1ORCID,Segawa Takuya F.2,Bütikofer Matthias1,Decker Venita3,Loss Sandra4,Czarniecki Barbara4,Torres Felix15ORCID,Riek Roland1ORCID

Affiliation:

1. ETH Zürich Swiss Federal Institute of Technology Institute for Molecular Physical Science Vladimir-Prelog-Weg 2 8093 Zürich Switzerland

2. ETH Zürich Swiss Federal Institute of Technology Laboratory of Physical Chemistry Vladimir-Prelog-Weg 2 8093 Zürich Switzerland

3. Bruker BioSpin GmbH Rudolf-Plank-Strasse 23 76275 Ettlingen Germany

4. Bruker Switzerland AG Industriestrasse 26 8117 Fällanden Switzerland

5. NexMR GmbH Wiesenstrasse 10 A 8952 Schlieren Switzerland

Abstract

AbstractFragment‐based drug design is a well‐established strategy for rational drug design, with nuclear magnetic resonance (NMR) on high‐field spectrometers as the method of reference for screening and hit validation. However, high‐field NMR spectrometers are not only expensive, but require specialized maintenance, dedicated space, and depend on liquid helium cooling which became critical over the recurring global helium shortages. We propose an alternative to high‐field NMR screening by applying the recently developed approach of fragment screening by photoinduced hyperpolarized NMR on a cryogen‐free 80 MHz benchtop NMR spectrometer yielding signal enhancements of up to three orders in magnitude. It is demonstrated that it is possible to discover new hits and kick‐off drug design using a benchtop NMR spectrometer at low micromolar concentrations of both protein and ligand. The approach presented performs at higher speed than state‐of‐the‐art high‐field NMR approaches while exhibiting a limit of detection in the nanomolar range. Photoinduced hyperpolarization is known to be inexpensive and simple to be implemented, which aligns greatly with the philosophy of benchtop NMR spectrometers. These findings open the way for the use of benchtop NMR in near‐physiological conditions for drug design and further life science applications.

Funder

Eidgenössische Technische Hochschule Zürich

Verein fur Krebsforschung

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

Publisher

Wiley

Subject

General Chemistry,Catalysis

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3