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

Abstract

We observed gelation of a 23-residue peptide derived from the beta-sheet domain of platelet factor-4 (PF4(24)(-)(46)). The gels were primarily heterogeneous mixtures of 50-200 microm 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 beta-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 degrees C but only 30 min at T >/= 50 degrees 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 beta-fibril gelation mechanisms.