| Texto completo | |
| Autor(es): |
Cianni, Lorenzo
[1]
;
Rocho, Fernanda dos Reis
[1]
;
Rosini, Fabiana
[1]
;
Bonatto, Vinicius
[1]
;
Ribeiro, Jean F. R.
[1]
;
Lameira, Jeronimo
[1]
;
Leitao, Andrei
[1]
;
Shamim, Anwar
[1]
;
Montanari, Carlos A.
[1]
Número total de Autores: 9
|
| Afiliação do(s) autor(es): | [1] Univ Sao Paulo, Inst Chem Sao Carlos, Med & Biol Chem Grp, Ave Trabalhador Sancarlense 400, BR-23566590 Sao Carlos, SP - Brazil
Número total de Afiliações: 1
|
| Tipo de documento: | Artigo Científico |
| Fonte: | BIOORGANIC CHEMISTRY; v. 101, AUG 2020. |
| Citações Web of Science: | 1 |
| Resumo | |
Cysteine proteases (CPs) are involved in a myriad of actions that include not only protein degradation, but also play an essential biological role in infectious and systemic diseases such as cancer. CPs also act as biomarkers and can be reached by active-based probes for diagnostic and mechanistic purposes that are critical in health and disease. In this paper, we present the modulation of a CP panel of parasites and mammals (Trypanosoma cruzi cruzain, LmCPB, CatK, CatL and CatS), whose inhibition by nitrile peptidomimetics allowed the identification of specificity and selectivity for a given CP. The activity cliffs identified at the CP inhibition level are useful for retrieving trends through multiple structure-activity relationships. For two of the cruzain inhibitors (10g and 4e), both enthalpy and entropy are favourable to Gibbs binding energy, thus overcoming enthalpy-entropy compensation (EEC). Group contribution of individual molecular modification through changes in enthalpy and entropy results in a separate partition on the relative differences of Gibbs binding energy (Delta Delta G). Overall, this study highlights the role of CPs in polypharmacology and multi-target screening, which represents an imperative trend in the actual drug discovery effort. (AU) | |
| Processo FAPESP: | 13/18009-4 - Planejamento, síntese e atividade tripanossomicida de inibidores covalentes reversíveis da enzima cruzaína |
| Beneficiário: | Carlos Alberto Montanari |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 16/07946-5 - Síntese e atividade tripanossomicida de potenciais inibidores covalentes reversíveis da enzima cruzaína |
| Beneficiário: | Lorenzo Cianni |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |
| Processo FAPESP: | 18/03985-1 - Planejamento, síntese e atividade tripanossomicida de inibidores covalentes reversíveis da enzima cruzaína |
| Beneficiário: | Anwar Shamim |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |