Aqueous gel formation of a synthetic peptide derived from the β-sheet domain of platelet factor-4

We observed gelation of a 23-residue peptide derived from the β-sheet domain of platelet factor-4 (PF4_24-46). The gels were primarily heterogeneous mixtures of 50-200 μm spherical aggregates in a less-dense gel matrix. Infrared and circular dichroism spectroscopies showed gelation involving the conversion of PF4_24-46 from random coil to β-sheet. We used aggregation-induced NMR resonance broadening to show that temperature, pH, and ionic strength influenced PF4_24-46 gelation rates. Under identical solution conditions, gel formation took days at T ≤ 20 °C but only 30 min at T ≥ 50 °C. Gelation was most rapid at pH values near the pK_a of the central His35 residue. Increases in solution ionic strength reduced the critical gelation concentration of PF4_24-46. Our results suggest that PF4_24-46 gels by a process combining aspects of both heat-set and β-fibril gelation mechanisms.