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10.1073/pnas.2005447117 http://scihub22266oqcxt.onion/10.1073/pnas.2005447117 32641511!7382296!32641511     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=32641511&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Proc+Natl+Acad+Sci+U+S+A 2020 ; 117 (29): 16782-16789 Nephropedia Template TP {{tp|p=32641511|t=2020. Discovery of potent thrombin inhibitors from a protease-focused DNA-encoded chemical library |pdf=|usr=}}{{32641511}} gab.com Text Discovery of potent thrombin inhibitors from a protease-focused DNA-encoded chemical library JO: Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=32641511 #FOAvip DNA-encoded chemical libraries are collections of compounds individually coupled to unique DNA tags serving as amplifiable identification barcodes. By bridging split-and-pool combinatorial synthesis with the ligation of unique encoding DNA oligomers, million- to billion-member libraries can be synthesized for use in hundreds of healthcare target screens. Although structural diversity and desirable molecular property ranges generally guide DNA-encoded chemical library design, recent reports have highlighted the utility of focused DNA-encoded chemical libraries that are structurally biased for a class of protein targets. Herein, a protease-focused DNA-encoded chemical library was designed that utilizes chemotypes known to engage conserved catalytic protease residues. The three-cycle library features functional moieties such as guanidine, which interacts strongly with aspartate of the protease catalytic triad, as well as mild electrophiles such as sulfonamide, urea, and carbamate. We developed a DNA-compatible method for guanidinylation of amines and reduction of nitriles. Employing these optimized reactions, we constructed a 9.8-million-membered DNA-encoded chemical library. Affinity selection of the library with thrombin, a common protease, revealed a number of enriched features which ultimately led to the discovery of a 1 nM inhibitor of thrombin. Thus, structurally focused DNA-encoded chemical libraries have tremendous potential to find clinically useful high-affinity hits for the rapid discovery of drugs for targets (e.g., proteases) with essential functions in infectious diseases (e.g., severe acute respiratory syndrome coronavirus 2) and relevant healthcare conditions (e.g., male contraception). Twit Text FOAVip Discovery of potent thrombin inhibitors from a protease-focused DNA-encoded chemical library ????Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=32641511 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32641511 #FOAvip English Wikipedia <ref>{{Cite pmid|32641511}}</ref> Discovery of potent thrombin inhibitors from a protease-focused DNA-encoded chemical library #MMPMID32641511 Dawadi S; Simmons N; Miklossy G; Bohren KM; Faver JC; Ucisik MN; Nyshadham P; Yu Z; Matzuk MM Proc Natl Acad Sci U S A 2020[Jul]; 117 (29): 16782-16789 PMID32641511show ga DNA-encoded chemical libraries are collections of compounds individually coupled to unique DNA tags serving as amplifiable identification barcodes. By bridging split-and-pool combinatorial synthesis with the ligation of unique encoding DNA oligomers, million- to billion-member libraries can be synthesized for use in hundreds of healthcare target screens. Although structural diversity and desirable molecular property ranges generally guide DNA-encoded chemical library design, recent reports have highlighted the utility of focused DNA-encoded chemical libraries that are structurally biased for a class of protein targets. Herein, a protease-focused DNA-encoded chemical library was designed that utilizes chemotypes known to engage conserved catalytic protease residues. The three-cycle library features functional moieties such as guanidine, which interacts strongly with aspartate of the protease catalytic triad, as well as mild electrophiles such as sulfonamide, urea, and carbamate. We developed a DNA-compatible method for guanidinylation of amines and reduction of nitriles. Employing these optimized reactions, we constructed a 9.8-million-membered DNA-encoded chemical library. Affinity selection of the library with thrombin, a common protease, revealed a number of enriched features which ultimately led to the discovery of a 1 nM inhibitor of thrombin. Thus, structurally focused DNA-encoded chemical libraries have tremendous potential to find clinically useful high-affinity hits for the rapid discovery of drugs for targets (e.g., proteases) with essential functions in infectious diseases (e.g., severe acute respiratory syndrome coronavirus 2) and relevant healthcare conditions (e.g., male contraception). |*Drug Discovery[MESH] |*Gene Library[MESH] |Combinatorial Chemistry Techniques[MESH] |DNA/*chemistry/*metabolism[MESH] |Humans[MESH] |Protease Inhibitors/chemistry/*pharmacology[MESH] |Small Molecule Libraries/chemistry/*pharmacology[MESH]Discovery of potent thrombin inhibitors from a protease-focused DNA-en(epmc).pdf DeepDyve Pubget Overpricing