Identification of a Small Secretoneurin Derivative That Inhibits CaMKIIδ Activity.

ABSTRACT: Ventricular arrhythmias, a major cause of sudden cardiac death, are driven by Ca²⁺ imbalance in cardiac myocytes, often linked to the overactivation of CaMKIIδ (Ca²⁺/calmodulin-dependent protein kinase II delta). As such, inhibiting CaMKIIδ represents a promising therapeutic strategy. Based on our previous finding that native secretoneurin (SN) is a weak CaMKIIδ inhibitor, we aimed to develop a more potent derivative of SN to effectively counter aberrant Ca²⁺ handling and arrhythmia risk. Various regions of SN were tested for CaMKII binding, identifying the core region as the sequence with the strongest binding capacity. This region was subsequently optimised with two phenylalanine substitutions, resulting in the SN derivative SN-db-short. Structural homolo

SUBMITTER: Rugolo I 

PROVIDER: S-EPMC12544700 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature