As mentioned in Section 1, once a given medical procedure in which heparin is used for clotting prevention is concluded, there is the immediate need to neutralize the polyanion anti-coagulant effect to allow blood clotting and recovery to begin. This is achieved by treating the patient with the only FDA approved heparin reversal compound, protamine, which requires a rigorous and personalized administration to avoid, or at least, minimize the deleterious side-effects. Therefore, a protamine replacer which, in addition to the required heparin binding characteristics, can safely degrade into non-toxic components if administered in excess could represent an ideal alternative heparin antidote. As it can be noticed from Figure 3a, the C22G1 molecular structure features one ester group in its central, linker part, which was incorporated by design with the idea of making this dendritic scaffold degradable via hydrolysis of this moiety in the presence of biological triggers (e.g., pH or esterases). We also surmised that, should our G22G1 dendron break down over time in a controllable and predictable way into smaller subunits, this could ultimately enhance its biocompatibility, lower its toxicity, and limit its persistence in cells. Moreover, dendron degradation would also disassemble the multivalent heparin binding array, thereby acting as an effective way of “switching off” its biological activity. To verify whether our molecular design and the underlying hypotheses were correct, we conducted an electrospray mass spectrometry (ESMS)-based assay to probe the pathways of dendron degradation which were actually taking place at pH = 7.4 [15,21]. While at the initial stages of the experiment the molecular ions associated with the intact C22G1 molecule (Figure 4a) were clearly visible after 24 h they completely disappeared, the dominant peaks in the spectra being those corresponding to the ester hydrolysis products (see Figure 4b).