Protegrin

Protegrin derivatives, 18 260 Protegrins, 18 260-261 properties of, 18 261 Protein. See also Proteins extraction of, 26 474 in cereal grains, 26 275-276 Proteinaceous materials, as membrane foulants, 21 664 Protein adsorption, 12 136-137 Protein affinity libraries, 12 516-517 Protein-based chiral phases, 6 89-90 Protein-based microarrays, 16 382 Protein biosynthesis, 20 450... 

An example of a simple CZE method for peptide analysis and characterization is the one developed for protegrin IB-367.37 IB-367 is a peptide containing 17 amino acid residues that possess antimicrobial properties, and it is being developed for treatment of oral mucositis associated with aggressive cancer chemotherapy as well as other topical applications. This polycationic product was chemically synthesized using solid-phase and purified by preparative reversed-phase HPLC. IB-367 is rich in cysteine and arginine residues. 

In mammals, two groups of host defense peptides are prominent the cathelicidins (notably human LL-37, porcine protegrin, and bovine indolicidin) and the defensins (human a- and /3-defensins). These two classes of peptides are involved in both intracellular and extracellular defensive responses and as individual peptides can be synthesized and stored in either active or inactive form within cells or secreted through degranulation into the surrounding environment. ... 

Figure 2 Selected stmctures of select host defense peptides representing the major structural classes (a) /3-sheet class (HNP-3 PDB1DFN) (b) linear a-helical class (magainin PDB2MAG) (c) extended class (indolicidin 1G89) (d) cysteine-stabilized 0-/3 (protegrin-3 1PFP). All stmctures were made with MOLMol and the color schema are as follows red/yellow, o-helical propensity aqua, /3-sheet propensity gray, extended or coil.

Protegrin-1 Porcine leukocyte RGGRLC Y CRRRFC V C V GR (3-Sheet 0.75-11 1.7-8 (64-66)... 

Ostberg Multiple linear regression 5(18) Protegrin 1 derivatives... 

Fahrner, R.L, Dieckmann, T Harwig, S.S.L., Lehrer, R.I., Eisenberg, D and Feigon, J. (1996) Solution structure of protegrin-1, a broad-spectrum antimicrobial peptide from porcine leukocytes. Chem. Biol. (London) 3, 543-550. 

Steinberg, D.A., Hurst, M.A., Jufii, C.A., et al. (1997) Protegrin-1 a broad-spectrum, rapidly microbicidal peptide with in vivo activity. Antimicrob. Agents Chemother. 41, 1738-1742. 

Frece, V. (2006) QSAR analysis of antimicrobial and haemolytic effects of cyclic cationic antimicrobial peptides derived from protegrin-1. Bioorgan. Medic. Chem. 14, 6065-6074. 

Ostberg, N., and Kaznessis, Y. (2004) Protegrin structure-activity relationships using homology models of synthetic sequences to determine structural characteristics important for activity. Peptides 26, 197-206. 

P NMR was also used to study of the oriented membranes and pores induced by protegrin-1 (PG-1), which represents AMPs.92,93 The line shape specifies the toroidal pores and thinned membranes that are formed in membrane bilayers by the binding of AMPs. The lateral diffusion of lipids were analysed from the motion-ally averaged 2D 31P SS NMR spectra. The mechanism of pore formation due to interaction between the peptide (fallaxidin) with lipids has been investigated.94... 

Several cyclic peptides have between two and eight cysteine residues. They adopt a triple-stranded 3-sheet structure e.g. vertebrate defensins) or a P-hairpin-like structure (e.g thanatin, androctonin, gomesin, and tachyplesin from arthropods and protegrin from vertebrate) or a mixed a-helix/p-sheet conformation (e.g. invertebrate and plant defensins, including some vertebrate defensins). Several reviews have been published in the past years discussing the structure and the mode of action of cyclic AMPs from animals. The reader is referred to the reviews written by Powers and Hancock [108], Bulet et al. [4], Ganz [8], and Yount [88]. In this chapter, only cyclic peptides with a P-hairpin-like structure will be discussed. 

The hairpin-like structure has been conserved in the course of evolution, since it was found in many peptides isolated from various classes of arthropods, such as the primitive horseshoe crabs (tachyplesins [110,111] and polyphemusins [112,113]), arachnids (androctonin in scorpion [114] and gomesin in spider [115]) insect (thanatin [116]), in two classes of vertebrates, mammalian (protegrin [117,118], lactoferricin B [119] and hepcidins [120]) and fish (hepcidins [121]), and in plants (76-AMPl[122]). 

Contrasting to thanatin and lactoferricin B, tachyplesins [110,111] and polyphemusins [112,113], androctonin [114] from the scorpion Androctonus australis, gomesin from the spider Acanthoscurria gomesiana [115], protegrin from porcine leukocytes [117,118], and 7 -AMPl from the plant Impatiens balsamina [122], have four cysteine residues in their sequenees. They all fold into a double-stranded antiparallel P-sheet structure. 

The role of the stereochemical configuration has been evaluated in several 3-hairpin-like peptides. For example, D enantiomers proved to be as potent as the native molecules in the cases of androctonin [128], protegrin 1 [133], and gomesin [134], implying that the peptides do not act via a stereo-specific receptor. 

Chen J, Fausnaugh-Pollitt J, Gu L (1999). Development and validation of a capillary electrophoresis method for the characterization of protegrin IB-367. J. Chromatog. A. 853 197-206. 

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