Going beyond Binary: Rapid Identification of Protein-Protein Interaction Modulators Using a Multifragment Kinetic Target-Guided Synthesis Approach.
Going beyond Binary: Rapid Identification of Protein-Protein Interaction Modulators Using a Multifragment Kinetic Target-Guided Synthesis Approach.
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DOI：
10.1021/acs.jmedchem.3c00108
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发表时间：
2023-04-13
影响因子：
7.3
通讯作者：
Manetsch, Roman
中科院分区：
文献类型：
--
作者：
Nacheva, Katya;Kulkarni, Sameer S.;Kassu, Mintesinot;Flanigan, David;Monastyrskyi, Andrii;Iyamu, Iredia D.;Doi, Kenichiro;Barber, Megan;Namelikonda, Niranjan;Tipton, Jeremiah D.;Parvatkar, Prakash;Wang, Hong-Gang;Manetsch, Roman
Kinetic target-guided synthesis (KTGS) is a powerful screening approach that enables identification of small molecule modulators for biomolecules. While many KTGS variants have emerged, a majority of the examples suffer from limited throughput and a poor signal/noise ratio, hampering reliable hit detection. Herein, we present our optimized multifragment KTGS screening strategy that tackles these limitations. This approach utilizes selected reaction monitoring liquid chromatography tandem mass spectrometry for hit detection, enabling the incubation of 190 fragment combinations per screening well. Consequentially, our fragment library was expanded from 81 possible combinations to 1710, representing the largest KTGS screening library assembled to date. The expanded library was screened against Mcl-1, leading to the discovery of 24 inhibitors. This work unveils the true potential of KTGS with respect to the rapid and reliable identification of hits, further highlighting its utility as a complement to the existing repertoire of screening methods used in drug discovery.
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小分子对胰岛素降解酶的催化位点诱导小鼠葡萄糖不耐症。
影响因子：
16.6
作者：
Deprez-Poulain R;Hennuyer N;Bosc D;Liang WG;Enée E;Marechal X;Charton J;Totobenazara J;Berte G;Jahklal J;Verdelet T;Dumont J;Dassonneville S;Woitrain E;Gauriot M;Paquet C;Duplan I;Hermant P;Cantrelle FX;Sevin E;Culot M;Landry V;Herledan A;Piveteau C;Lippens G;Leroux F;Tang WJ;van Endert P;Staels B;Deprez B
通讯作者：
Deprez B
影响因子：
3.3
作者：
Hirose, Tomoyasu;Sunazuka, Toshiaki;Omura, Satoshi
通讯作者：
Omura, Satoshi
影响因子：
3.4
作者：
Mocharla, Vani P.;Walsh, Joseph C.;Kolb, Hartmuth C.
通讯作者：
Kolb, Hartmuth C.
DOI：
10.1002/chem.202002250
发表时间：
2020-11-17
期刊：
Chemistry (Weinheim an der Bergstrasse, Germany)
影响因子：
--
作者：
Mancini F;Unver MY;Elgaher WAM;Jumde VR;Alhayek A;Lukat P;Herrmann J;Witte MD;Köck M;Blankenfeldt W;Müller R;Hirsch AKH
通讯作者：
Hirsch AKH
影响因子：
16.6
作者：
Bhardwaj A;Kaur J;Wuest M;Wuest F
通讯作者：
Wuest F