Antimicrobial defensin peptide folding variants

A composition comprising a Defensin peptide folding variant 1 (DEF_PFV1),

• wherein said Defensin peptide is a synthetic variant of a native Defensin peptide comprising in contiguous amino acid sequence from its N-terminal end (1) a first amino acid pair motif including X1 and C2, (2) a first intervening sequence (IS1), (3) a first cysteine pair motif including C3 and C4, (4) a second intervening sequence (IS2), (5) a second cysteine pair motif including C5 and C6, (6) a third intervening sequence (IS3), and (7) a second amino acid pair motif including C7 and Y1,
• wherein said amino acid X1 and Y1 are each independently selected from the group of amino acids other than cysteine, and
• wherein cysteines C2, C3, C4, C5, C6, and C7 of DEF_PFV1 form a first set of disulfide bonds and DEF_PFV1 thereby adopts a first conformation that exhibits greater antimicrobial activity increased protease resistance, or increased protease sensitivity as compared to a Defensin peptide folding variant 2 (DEF_PFV2) that has the same amino acid sequence as DEF_PFV1 but forms a distinct second set of disulfide bonds between cysteines C2, C3, C4, C5, C6, and C7 and adopts a distinct second conformation, and
• wherein said composition is substantially free of DEF_PFV2.

A composition comprising a Defensin peptide folding variant 1 (DEF_PFV1),

• wherein said Defensin peptide is a synthetic variant of a native Defensin peptide comprising in contiguous amino acid sequence from its N-terminal end (1) a first amino acid pair motif including X1 and Y1, (2) a first intervening sequence (IS1), (3) a first cysteine pair motif including C3 and C4, (4) a second intervening sequence (IS2), (5) a second cysteine pair motif including C5 and C6, (6) a third intervening sequence (IS3), and (7) a second amino acid pair motif including X2 and Y2,
• wherein said amino acids X1, Y1, X2, and Y2 are each independently selected from the group of amino acids other than cysteine, and
• wherein cysteines C3, C4, C5, and C6 of DEF_PFV1 form a first set of disulfide bonds and DEF_PFV1 thereby adopts a first conformation that exhibits greater antimicrobial activity, increased protease resistance, or increased protease sensitivity as compared to a Defensin peptide folding variant 2 (DEF_PFV2) that has the same amino acid sequence as DEF_PFV1 but forms a distinct second set of disulfide bonds between cysteines C3, C4, C5, and C6 and adopts a distinct second conformation, and
• wherein said composition is substantially free of DEF_PFV2.

A composition comprising a Defensin peptide folding variant 1 (DEF_PFV1),

• wherein said Defensin is a cationic Defensin peptide comprising a Defensin gamma core peptide sequence GXC5X3-9C6 (SEQ ID NO:
• 455) or variant gamma core peptide sequence GXC5X3-10C6 (SEQ ID NO:
• 456), GXC5X3-9 (F/W/Y) (SEQ ID NO:
• 457), or GXC5X3-10 (F/W/Y) (SEQ ID NO:
• 458) and at least two or three additional cysteine residues selected from the group consisting of cysteine residues corresponding to C1, C2, C3, C4, C7, and C8 of a reference Defensin peptide,
• wherein said cysteine residues of DEF_PFV1 form a first set of disulfide bonds and DEF_PFV1 thereby adopts a first conformation that exhibits greater antimicrobial activity, increased protease resistance, or increased protease sensitivity as compared to a Defensin peptide folding variant 2 (DEF_PFV2) that has the same amino acid sequence as DEF_PFV1 but forms a distinct second set of disulfide bonds between cysteine residues and adopts a distinct second conformation, and
• wherein said composition is substantially free of DEF_PFV2.