Dillon T Flood1, Xuejing Zhang1,2, Xiang Fu1,2, Zhenxiang Zhao1, Shota Asai3, Brittany B Sanchez4, Emily J Sturgell4, Julien C Vantourout1, Paul Richardson5, Mark E Flanagan6, David W Piotrowski6, Dominik K Kölmel6, Jinqiao Wan7, Mei-Hsuan Tsai7, Jason S Chen4, Phil S Baran1, Philip E Dawson1. 1. Department of Chemistry, Scripps Research, 10550 N. Torrey Pines Road, La Jolla, CA, 92037, USA. 2. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China. 3. Department of Chemistry and Biological Sciences, Faculty of and Engineering, Iwate University, 4-3-5 Ueda, Morioka, 020-8551, Japan. 4. Automated Synthesis Facility, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA, 92037, USA. 5. Pfizer Medicinal Chemistry, 10770 Science Center Drive, San Diego, CA, 92121, USA. 6. Pfizer Medicinal Chemistry, Eastern Point Road, Groton, CT, 06340, USA. 7. HitGen Inc., Building 6, No. 8 Huigu 1st East Road Tianfu International Bio-Town, Shuangliu District, Chengdu, 610200, Sichuan, China.
Abstract
DNA encoded libraries (DEL) have shown promise as a valuable technology for democratizing the hit discovery process. Although DEL provides relatively inexpensive access to libraries of unprecedented size, their production has been hampered by the idiosyncratic needs of the encoding DNA tag relegating DEL compatible chemistry to dilute aqueous environments. Recently reversible adsorption to solid support (RASS) has been demonstrated as a promising method to expand DEL reactivity using standard organic synthesis protocols. Here we demonstrate a suite of on-DNA chemistries to incorporate medicinally relevant and C-S, C-P and N-S linkages into DELs, which are underrepresented in the canonical methods.
DNA encoded libraries (n class="Chemical">pan class="Chemical">DEL) have shown pn>romise as a valuable technology for democratizing the hit discovery process. Although DEL provides relatively inexpensive access to libraries of unprecedented size, their production has been hampered by the idiosyncratic needs of the encoding DNA tag relegating DEL compatible chemistry to dilute aqueous environments. Recently reversible adsorption to solid support (RASS) has been demonstrated as a promising method to expand DEL reactivity using standard organic synthesis protocols. Here we demonstrate a suite of on-DNA chemistries to incorporate medicinally relevant and C-S, C-P and N-S linkages into DELs, which are underrepresented in the canonical methods.
Authors: Łukasz Janczewski; Mateusz Psurski; Marta Świtalska; Anna Gajda; Tomasz M Goszczyński; Józef Oleksyszyn; Joanna Wietrzyk; Tadeusz Gajda Journal: ChemMedChem Date: 2017-12-06 Impact factor: 3.466
Authors: Zhoulong Fan; Shuai Zhao; Tao Liu; Peng-Xiang Shen; Zi-Ning Cui; Zhe Zhuang; Qian Shao; Jason S Chen; Anokha S Ratnayake; Mark E Flanagan; Dominik K Kölmel; David W Piotrowski; Paul Richardson; Jin-Quan Yu Journal: Chem Sci Date: 2020-09-07 Impact factor: 9.825