PMC:6723693 / 9324-10883 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/6723693","sourcedb":"PMC","sourceid":"6723693","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6723693","text":"From Figure 2a and Table A1 we see that the smallest dendrimer of the series (G0) is clearly not able to displace MB from the polysaccharide. On the other hand, as the dendrimer generation grows, the corresponding EC50 value decreases (from 10.10 µM of G1 to 0.22 µM of G6) by virtue of the increasing dendrimer surface charge leading to higher heparin/binder affinity. However, in terms of a given dendrimer’s ability to exploit each individual positive charge in heparin binding (CE50), the observed behavior is not monotonic, in that both the smallest (G1) and the biggest (G6) dendrimers are characterized by the worst (i.e., highest) EC50 value, while the other PAMAMs (G2–G4) exhibit better heparin binding performance in this respect (Table A1). An utterly analogous trend is observed when considering the ligand dose required to bind 100 IU of heparin (last column in Table A1). The touchstone molecule, protamine, is characterized by an EC50 value of 2.34 µM, a CE50 of 0.52, and a corresponding dose of 0.32 mg/100 heparin IU (Table A1). Therefore, a global reconsideration of all values listed in Table A1 leads to the conclusion that the most promising protamine replacer among the entire PAMAM dendrimer series considered is G2, not only because its heparin binding parameter set (EC50 = 2.55 µM and CE50 = 0.38) and dosage required (0.25 mg/100 heparin IU) most favorably compare with those characterizing the small arginine-based protein but also because low generation dendrimers are generally endowed with lower in vivo toxicity effects [35].","tracks":[]}