Retrocyclins are circular mini-defensins with significant potential as agents against human immunodeficiency virus, influenza A, and herpes simplex virus. Retrocyclins bind carbohydrate-containing surface molecules such as gp120 and CD4 with high affinity (Kd, 10-100 nM), promoting their localization on cell membranes. The structural features important for activity have yet to be fully elucidated, but here, we have determined the first three-dimensional structure of a retrocyclin, namely, one of the most potent forms, retrocyclin-2. In the presence of SDS micelles, a well-defined beta-hairpin braced by three disulfide bonds that defines the cystine ladder motif is present. By contrast, a well-defined structure could not be determined in aqueous solution, suggesting that the presence of SDS micelles stabilizes the extended conformation of retrocyclin-2. Translational diffusion measurements indicate that retrocyclin-2 interacts with the SDS micelles, and such a membrane-like interaction may be an important feature in the mechanism of action of these antimicrobial peptides. Analytical ultracentrifugation and the NMR data indicated that retrocyclin-2 self-associates to form a trimer in a concentration-dependent manner. The ability to self-associate may contribute to the high-affinity binding of retrocyclins for glycoproteins by increasing the valency and enhancing the ability of retrocyclins to cross-link cell surface glycoproteins.

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Leakage of plasma proteins into the alveoli inhibits pulmonary surfactant function and worsens respiratory failure. Surfactant protein B (SP-B), is essential for surfactant function, but the N-terminal domain of human SP-B (residues 1.25, SP-B 1±25 ) can mimic the biophysical properties of full length SP-B 1±78 in vitro.The authors compared the function and inhibition resistance of synthetic surfactant preparations containing SP-B analogues to a natural bovine surfactant preparation "Survanta TM ".Eight groups of eight rats were lavaged to induce surfactant deficiency, fibrinogen was instilled as a surfactant inhibitor, and then they were rescued with exogenous surfactant. Five experimental surfactants were formulated by mixing 3% SP-B 1±78 , or an equimolar amount of SP-B 1±25 and/or 1% palmitoylated surfactant protein C (SP-C) 1±35 , into a standard phospholipid (PL) mixture: B 1±78 , B 1±25 , C 1±35 , B 1±78 +C 1±35 , and B 1±25 +C 1±35 surfactant preparations. Survanta TM was used as a positive control and PL and no treatment as a negative control. Lung function was assessed during a 2-h period using arterial blood gas and lung compliance measurements.Rats treated with B 1±25 +C 1±35 surfactant and Survanta TM maintained the highest oxygenation and lung compliance values throughout the experiments. The surfactants could be ranked as B 1±25 +C 1±35 surfactant and Survanta TM >B 1±25 and B 1±78 +C 1±35 surfactants >others.

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