Calcium-Mobilizing Behaviors of Neutral Cyclic ADP-Ribose Mimics that Integrate Modifications to the Nucleobase, Northern Ribose and Pyrophosphate.
Chembiochem
; 19(13): 1444-1451, 2018 07 04.
Article
em En
| MEDLINE
| ID: mdl-29633462
ABSTRACT
Cyclic adenosine diphosphate ribose (cADPR) is an endogenous Ca2+ mobilizer involved in diverse cellular processes. Mimics of cADPR play a crucial role in investigating the molecular mechanism(s) of cADPR-mediated signaling. Here, compound 3, a mimic of cADPR in which a neutral triazole moiety and an ether linkage were introduced to substitute the pyrophosphate and "northern" ribose components, respectively, was synthesized for the first time. The pharmacological activities in Jurkat cells indicated that this mimic is capable of penetrating plasma membrane and inciting Ca2+ release from the endoplasmic reticulum (ER) through the action of ryanodine receptors (RyRs) and triggering Ca2+ influx. Furthermore, a uridine moiety was introduced in place of adenine and the new cADPR mimics 4 and 5 were synthesized. The results of biological investigation showed that these mimics also targeted RyRs and retained moderate Ca2+ agonistic activities. The results indicated that the neutral cADPR mimics had the same targets for inducing Ca2+ signaling.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Triazóis
/
Cálcio
/
Sinalização do Cálcio
/
ADP-Ribose Cíclica
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article