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Synthetic melanin polymers with antithrombotic activity (833.3)
Author(s) -
Holmes Earle
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.833.3
Subject(s) - polymerization , chemistry , chromogenic , thrombin , fibrin , hydrolysis , coagulation , polymer , biochemistry , antithrombotic , chromatography , polymer chemistry , nuclear chemistry , organic chemistry , immunology , platelet , biology , medicine
I evaluated the anticoagulant properties of a family of novel water soluble melanin polymers (Mels) synthesized by a patented process (12/809,369). Mels were screened for activity in standard assays for the measurement of the PT, the aPTT and the TT. Active Mels were further investigated by the evaluation of the kinetics of fibrin polymerization and the re‐polymerization of fibrinopeptides, and for the direct inhibition of factors Xa and thrombin. Ten of the Mels prolonged the aPTT and the TT by more than 2‐ fold (aPTT: mean, 3.7‐fold, range, 2.1‐6.7; TT: mean, 8‐fold, range, 2.1‐15). Mels C1, C12, EM and CAM (2.5 to 41mcg/mL) caused dose‐dependent delays in the onset, rate, and extent of thrombin‐mediated fibrinogenesis in the presence and absence of Ca++. Mels C1 and C12 inhibited the re‐polymerization of fibrinopeptides at high doses, but increased the rate and extent of re‐polymerization at low doses. Mels minimally inhibited factor Xa activity in a chromogenic assay, whereas Mels C1, EM, and C12 inhibited the hydrolysis of a chromogenic thrombin substrate by 49%, 39%, and 28%, respectively. Mels inhibit the common pathway of coagulation by multiple mechanisms. These activities, in conjunction with the high chemical reactivity of the intermediates that are generated during Mel synthesis may provide a new approach to the incorporation anti‐thrombotic properties into biomaterials.