WEDNESDAY, May 26 (HealthDay News) -- A new investigation of synthetic fibrin knob peptide structures in solution and their dynamic binding with fibrinogen/fibrin holes may lead to a more thorough knowledge of fibrin assembly mechanisms, and establish criteria for designing anticoagulants that can inhibit fibrin assembly associated with heart attack, stroke and tissue damage, according to a study published online May 18 in Blood.
Sarah E. Stabenfeldt, Ph.D., of Emory University in Atlanta, and colleagues measured the hole binding characteristics of six knob sequences -- each of which was seven or eight amino acids long -- to evaluate the impact of additional backbone stabilization and/or different charge distributions.
The researchers found that binding rates improved significantly when they added two amino acids (proline and phenylalanine) for stabilization and by having charged configurations in the sixth and seventh positions in the sequences. They also identified a novel knob peptide mimic (GPRPFPAC) that has a binding rate to holes that is one order of magnitude higher than previously published knob sequences, and surpasses the binding activity of the gold standard mimic (GPRPAAC).
"These findings provide insights into early fibrin protofibril assembly dynamics as well as establish essential design parameters for high affinity knob mimics that more efficiently compete for hole occupancy, parameters realized here through a novel knob mimic displaying a 10-fold higher association rate than current mimics," the authors conclude.
Abstract
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