Metabolically stable apelin-analogues, incorporating cyclohexylalanine and homoarginine, as potent apelin receptor activators.

ABSTRACT: High blood pressure and consequential cardiovascular diseases are among the top causes of death worldwide. The apelinergic (APJ) system has emerged as a promising target for the treatment of cardiovascular issues, especially prevention of ischemia reperfusion (IR) injury after a heart attack or stroke. However, rapid degradation of the endogenous apelin peptides in vivo limits their use as therapeutic agents. Here, we study the effects of simple homologue substitutions, i.e. incorporation of non-canonical amino acids l-cyclohexylalanine (l-Cha) and l-homoarginine (l-hArg), on the proteolytic stability of pyr-1-apelin-13 and apelin-17 analogues. The modified 13-mers display up to 40 times longer plasma half-life than native apelin-13 and in preliminary in vivo assay sho

SUBMITTER: Fernandez KX 

PROVIDER: S-EPMC8372210 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature