Anti-S2 peptides target cardiac myosin for in vivo responses

Abstract

Chemically synthesized peptides designed to modulate the unfolding of cardiac myosin S2 were conjugated to heart targeting molecule for injection into live mice. Fluorescently labeled peptides confirmed that some of the peptides reached the heart. Fluorescence detected by superresolution microscopy in the walls of the coronary artery, extracellular matrix, t-tubules, and sarcomeres suggested a possible route for the peptides reaching the myosin S2 in vivo. Echocardiography measurements indicated that IV injection of 20 nmol of the fluorescently labeled Destabilizer peptide that induces an unfolded conformation of the myosin S2 led to a statistically significant increase in cardiac output in 24 hrs.