About: Structural basis for the development of SARS 3CL protease inhibitors from a peptide mimic to an aza‐decaline scaffold

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About: Structural basis for the development of SARS 3CL protease inhibitors from a peptide mimic to an aza‐decaline scaffold Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Structural basis for the development of SARS 3CL protease inhibitors from a peptide mimic to an aza‐decaline scaffold
Creator	Akaji, Kenichi Teruya, Kenta Hattori, Yasunao Kobayashi, Kazuya Nakagawa, Atsushi Sanjoh, Akira Shimamoto, Yasuhiro Yamashita, Eiki
Source	Medline; PMC
abstract	Design of inhibitors against severe acute respiratory syndrome (SARS) chymotrypsin‐like protease (3CL(pro)) is a potentially important approach to fight against SARS. We have developed several synthetic inhibitors by structure‐based drug design. In this report, we reveal two crystal structures of SARS 3CL(pro) complexed with two new inhibitors based on our previous work. These structures combined with six crystal structures complexed with a series of related ligands reported by us are collectively analyzed. To these eight complexes, the structural basis for inhibitor binding was analyzed by the COMBINE method, which is a chemometrical analysis optimized for the protein–ligand complex. The analysis revealed that the first two latent variables gave a cumulative contribution ratio of r(2) = 0.971. Interestingly, scores using the second latent variables for each complex were strongly correlated with root mean square deviations (RMSDs) of side‐chain heavy atoms of Met(49) from those of the intact crystal structure of SARS‐3CL(pro) (r = 0.77) enlarging the S(2) pocket. The substantial contribution of this side chain (∼10%) for the explanation of pIC(50)s was dependent on stereochemistry and the chemical structure of the ligand adapted to the S(2) pocket of the protease. Thus, starting from a substrate mimic inhibitor, a design for a central scaffold for a low molecular weight inhibitor was evaluated to develop a further potent inhibitor. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 391–403, 2016.
has issue date	2016-07-22(xsd:dateTime)
bibo:doi	10.1002/bip.22773
bibo:pmid	26572934
has license	no-cc
sha1sum (hex)	aa479011d0dd94d2676a199dd060c45b6d26e42c
schema:url	https://doi.org/10.1002/bip.22773
resource representing a document's title	Structural basis for the development of SARS 3CL protease inhibitors from a peptide mimic to an aza‐decaline scaffold
has PubMed Central identifier	PMC7159131
has PubMed identifier	26572934
schema:publication	Biopolymers
resource representing a document's body	covid:aa479011d0dd94d2676a199dd060c45b6d26e42c#body_text
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