Basically, HDPs can be classified according to four characteristic structures [6]: (1) β-sheet structures stabilized with two or three disulfide

bonds such as mammalian defensins, (2) amphipathic α-helical structures such as human cathelicidin (3) loop structures containing one disulfide bound such as dodecapeptide, and (4) extended structures such as PR-39 and histatins (Table 1) [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29] and [30]. Three families of HDPs are expressed predominantly in humans: defensins, cathelicidin, and histatins. Defensins are small cysteine-rich HDPs that mainly form β-sheet structures stabilized by several (usually three) conserved intramolecular cysteine disulfide bounds and are typically 28–44 amino-acid

residues. GDC 0199 Three subfamilies, α-, β-, and θ-defensins, are expressed in vertebrates [9]. In humans, θ-defensin mRNA is expressed; however, lack the corresponding peptides since the human θ-defensin gene contains a stop codon in the signal sequence that aborts translation [31]. The insect and plant defensins contain six or eight cysteines in the disulfide bridge. In addition, insect defensins contain α-helical disulfide bridges connected to a β-sheet structure stabilized by cysteine, which differs from vertebrate defensins [9]. Cathelicidins comprise a large number of precursors of HDPs that typically contain a conserved N-terminal sequence region that shares high homology Z-VAD-FMK with the proregion of cathelin, a cathepsin L inhibitor (hence the term cath-e-L-in). The C-terminal antimicrobial domain of different cathelicidin precursors varies widely in terms of sequence, composition, and structure. Processed cathelicidin peptides range from 12 to 80 or more amino

acid residues in size and may have β-sheet, α-helical, loop, or extended structures [32] and [33] (Table 1). The only human cathelicidin, antimicrobial peptide LL-37, is composed of 37 amino acid residues and a cysteine-free peptide that can adopt an amphipathic α-helical conformation [34]. In contrast, histatins are family of 4��8C small cationic histidine-rich peptides amounting to 3–5 kDa in the human saliva [35]. The major family members of histatins 1 and 3 are products of human genes alone: these are HIS1 and HIS2, respectively [36]. Histatin 5 originates from histatin 3 by post-translational processing. Histatin 1, 3, and 5 have linear extended structures containing 38, 32, and 24 amino acid residues, respectively, and the sequence of the first 22 amino acids of each histatin is identical [37]. Cathelicidins were first discovered in mammals but have been recently found in chickens and three species of fish (rainbow trout, Atlantic salmon, and hagfish). In particular, hagfish remarkably lacks essential components of adaptive immunity.