Anti-ischemic effects of multivalent dendrimeric A₃ adenosine receptor agonists in cultured cardiomyocytes and in the isolated rat heart.

ABSTRACT: Adenosine released during myocardial ischemia mediates cardioprotective preconditioning. Multivalent drugs covalently bound to nanocarriers may differ greatly in chemical and biological properties from the corresponding monomeric agents. Here, we conjugated chemically functionalized nucleosides to poly(amidoamine) (PAMAM) dendrimeric polymers and investigated their effects in rat primary cardiac cell cultures and in the isolated heart. Three conjugates of A₃ adenosine receptor (AR) agonists, chain-functionalized at the C2 or N⁶ position, were cardioprotective, with greater potency than monomeric agonist Cl-IB-MECA. Multivalent amide-linked MRS5216 was selective for A₁ and A₃ARs, and triazole-linked MRS5246 and MRS5539 (optionally containing fluorescent label) were A₃AR-selective. The conju

SUBMITTER: Chanyshev B 

PROVIDER: S-EPMC3278557 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature