One Step Beyond: Design of substrates spanning primed positions of Zika virus NS2B-NS3 protease
Natalia Gruba , Jose Ignacio Rodriguez Martinez , Renata Grzywa , Magdalena Wysocka , Marcin Skoreński , Agnieszka Dabrowska , Maria Łęcka , Piotr Suder , Marcin Sieńczyk , Krzysztof Pyrc , Adam Lesner
AbstractAlthough the mosquito-borne Zika virus was discovered in the late 1940s of the 20th century, for years it was neglected, as the disease in humans was rare and relatively mild. Viral NS2B-NS3 protease is essential for virus replication, and except for maturation of viral proteins, it also modulates the infection microenvironment to facilitate virus invasion. Here, we report the combinatorial chemistry approach for the synthesis of internally quenched substrates of the Zika virus NS2B-NS3 protease that were optimized in prime positions of the peptide chain. Final substrate ABZ-Val- Lys-Lys-Arg-Ala-Ala-Trp-Tyr(3-NO 2 )-NH 2 displays an excel- lent kinetic parameter ( k cat / K M reaching nearly 1.26 × 10(8) M−1 × s−1), which is over 10 times greater than previously reported (7.7 × 10(6) M−1 × s−1) substrate. Moreover, it was found to be selective over West Nile virus protease.
|Journal series||ACS Medicinal Chemistry Letters, ISSN 1948-5875, (A 35 pkt)|
|Publication size in sheets||0.5|
|Keywords in English||Zika virus, NS2B-NS3 protease, internally quenched peptides, peptide library, combinatorial chemistry|
|Score|| = 35.0, 10-09-2018, ArticleFromJournal|
= 35.0, 10-09-2018, ArticleFromJournal
|Publication indicators||: 2016 = 3.746 (2) - 2016=3.594 (5)|
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