SMALL, ANIONIC, AND CHARGE-NEUTRALIZING PROPEPTIDE FRAGMENTS OF ZYMOGENS ARE ANTIMICROBIAL

Some inactive precursor proteins, or zymogens, contain small, amino te rminus, homopolymeric regions of Asp that neutralize the cationic char ge of the active protein during synthesis. After posttranslational cle avage, the anionic propeptide fragment may exhibit antimicrobial activ ity. To demonstrate this, ovine trypsinogen activation peptide, and fr og (Xenopus laevis) Pn activation peptide, both containing homopolymer ic regions of Asp, were synthesized and tested against previously desc ribed surfactant-associated anionic peptide. Peptides inhibited the gr owth of both gram-negative (MIC, 0.08 to 3.00 mM) and gram-positive (M IC, 0.94 to 2.67 mM) bacteria. Smalt, anionic, and charge-neutralizing propeptide fragments of zymogens form a new class of host-derived ant imicrobial peptides important in innate defense.