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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

versatile inhibitor of digestive enzymes in Aedes aegypti larvae selected from a pacifastin (TiPI) phage display librar

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Manzato, Veronica Moraes [1] ; Soares Torquato, Ricardo Jose [1] ; Alves Lemos, Francisco Jose [2, 3] ; Nishiduka, Erika [1] ; Tashima, Alexandre Keiji [1] ; Tanaka, Aparecida Sadae [3, 1]
Total Authors: 6
[1] Univ Fed Sao Paulo, Dept Bioquim, Escola Paulista Med, Rua 3 Maio 100, BR-04044020 Sao Paulo, SP - Brazil
[2] Univ Estadual Norte Fluminense, Lab Biotecnol, Rio De Janeiro, RJ - Brazil
[3] Inst Nacl Ciencia & Tecnol Entomol Mol INCT Em, Rio de Janeiro, RJ - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Biochemical and Biophysical Research Communications; v. 590, p. 139-144, JAN 29 2022.
Web of Science Citations: 0

In Brazil, the major vector of arboviruses is Aedes aegypti, which can transmit several alpha and flaviviruses. In this work, a pacifastin protease inhibitor library was constructed and used to select mutants for Ae. aegypti larvae digestive enzymes. The library contained a total of 3.25 x 10(5) cfu with random mutations in the reactive site (P2-P2'). The most successfully selected mutant, TiPI6, a versatile inhibitor, was able to inhibit all three Ae. aegypti larvae proteolytic activities, trypsin-like, chymotrypsin-like and elastase-like activities, with IC50 values of 0.212 nM, 0.107 nM and 0.109 nM, respectively. In conclusion, the TiPI mutated phage display library was shown to be a useful tool for the selection of an inhibitor of proteolytic activities combined in a mix. TiPI6 is capable of controlling all three digestive enzyme activities present in the larval midgut extract. To our knowledge, this is the first time that one inhibitor containing a Gln at the P1 position showed inhibitory activity against trypsin, chymotrypsin, and elastase-like activities. TiPI6 can be a candidate for further larvicidal studies. (C) 2021 Published by Elsevier Inc. (AU)

FAPESP's process: 12/03657-8 - Inhibitor and proteases of ectoparasites: relationship of structure-function and identification of the role of these molecules in the interaction of diseases vector e their etiological agents
Grantee:Aparecida Sadae Tanaka
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 19/03779-5 - Use of phage display as a tool in the diagnosis and control of diseases transmitted by hematophagous vectors
Grantee:Aparecida Sadae Tanaka
Support Opportunities: Research Projects - Thematic Grants