**1.5.4 θ defensins**

54 Antimicrobial Agents

The brevinin show alpha helical structure in sodium dodecyl sulfate solution (Lee et al., 2002). Antibacterial activity is favored by structure that group the cationic amino acids of the molecule with on one side an hydrophobic stretch of amino acids and on the other side streches of apolar amino acids (Kumari and Nagaraj, 2001). Liposome disruption activity of the brevinins correlates with the anti-Gram positive bacterial activity, suggesting a lytic activity. None of the peptides showed hemolytic activity making brevinins attractive

This class of peptide is characterized by its rigid structure, given by the presence of 3 to 4 disulfid bridges. They are sub-classified through their cysteines connectivity and their

By virtue of the cysteine knot motif that stabilize them, all these peptides show a rigid secondary structure. Defensin are amphipatic molecules with a common defined beta sheet motif secondary structure. Indeed there is a gamma-core motif (GXCX(3-9)C), considered the structural signature of the disulfide-stabilized antimicrobial peptides that present two beta strands with an interposed loop (Sagaram et al., 2011). This motif has one hydrophobic and one hydrophilic side. The hydrophilic side of these peptides is usually constituted by several lysine or arginine aminoacids. This gives them a general positive charge at physiological pH. They are resistant to degradation and peptidase digestion because of their compact structure. As for the other antimicrobial peptide classes, there are few phylogenetic relationships even within each defensin subclass. The first three defensins class described

This type of defensins is found in mammals. Their cysteine are connected between the cysteines 1-6 2-4 3-5. They show a structure of triple-stranded beta-sheet stabilized by a conserved triple disulfide bridges array (Hadjicharalambous et al., 2008). Alpha defensin sequence present more arginine than lysine residues, and it has been suggested that this high arginine content endows the alpha-defensin with a higher antibacterial activity in high

The beta defensin have a cysteine connectivity of 1-5 2-4 3-6. They present the consensus sequence of Xn-C-X2-4-G-X1-2-CX3-5CX9-10CX5-6CCXn (Ganz, 2003a) (C=cysteine and G=Glycine). They present a tri dimensional structure of a triple stranded beta sheet. The glycine invariant is also present in alpha defensin. This glycine is necessary for the beta bulge structure to be formed, and the protein is unable to fold if it is replaced by any other

*Sus scrofa* beta-defensin 1 SVSCLRNKGVCMPGKCAPKMKQIGTCGMPQVKCCKRK

*P. hamadryas* alpha-defensin ACYCRIPACFAGERRYGTCFYLGRVWAFCC

prospects for broad-spectrum antimicrobial peptide design (Lee et al., 2002).

**1.5 Defensins (cysteine knot structure)** 

were found exclusively in mammals.

salt conditions (Llenado et al., 2009).

natural amino acid (Xie et al., 2005).

**1.5.2 Alpha defensins** 

**1.5.3 Beta defensins** 

**1.5.1 General properties** 

secondary structure.

θ defensin are macrocyclic octadeca peptides connected head to tail. These peptides are present in monkeys but absent in human. There are θ-defensin ortholog pseudo genes in the human genome but the Theta-defensin genes contain a premature stop codon that aborts translation. (Cole et al., 2002) (Cole et al., 2004). Their synthesis implies a head to tail circularization of an octa-peptide (Selsted, 2004). They were found to be active against *S. aureus, E. coli, and C. albicans* as well as HIV virus (Cole et al., 2002). This type of defensins also present a disulfide bridges stabilized amphipathic beta sheet structure.

*P. hamadryas* theta-defensin-1 RCVCRRGVCRCVCTRGFC
