Bioactive Oligopeptides

Glutathione (L-y-glutamyl-L-cysteinyl-glycine, GSH) was released by rat pulmonary alveolar macrophages cultured in RPMI 1640 supplemented with 10% foetal cal/serum exposed for 2 h to 0-100 [tg quartz particles (Min-U-Sil, 4.5 1.0 p,m) or croci-dolite asbestos (lUAC, fibre length 2.1 0.31 [xm) in a concentration-dependent manner (Boehme et al. 1992). 

In plasma from 24 healthy individuals aged 25-35 years, Jones et al. (2000) found the concentration of GSH (2.8 0.9 M) much higher than that of GSSG (0.14 0.04 fiM). The redox potential of the 

GSSG/2GSH pool (-137 9 mV) was considerably more oxidised than values for tissues and cultured cells (-185 to -258 mV). This indicates that a rapid oxidation of GSH occurs upon release into plasma. The difference in values between individuals was remarkably small, suggesting that the rates of reduction and oxidation in the plasma are closely balanced to maintain this redox potential. 

Glutathione thiyl radicals (GS ) can be produced e.g. when radicals from oxidable drugs redox cycle (ScHREiBER et al. 1989), or in the repair of oxidative stress (O Brien 1988) and radiation damage (Quintiliani et al. 1977). 

The fate of GS depends critically on four key, rapidly estabhshed equihbria  

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I. Gill and R. Valivety, Pilot-scale enzymatic synthesis of bioactive oligopeptides in eutectic-based media, Org. Proc. Res. Dev. 2002, 6, 684-691. 

The major nutraceutical application of marine-derived bioactive peptides has been ACE inhibition, and a partial list of identified bioactive peptides is given in Table 27.1. Fish protein has been reported to be an advantageous starting material for preparation of ACE inhibitory peptide hydrolysates (Curtis et al., 2002). Marine-derived protein hydrolysate tends to contain high concentrations of cysteine, methionine, and arginine, all of which help reduce hypertension (Kristinsson, 2007). Such marine-derived peptides could be used as potent functional food additives and represent a healthier and natural alternative to ACE inhibitor drugs (Li et aL, 2004). Currently, the bioactive oligopeptides from dried bonito and sardine muscle have been approved as Foods for Specified Health Use by the Ministry of Health and Welfare in Japan. 

C. S. C. Wu, A. Hachimori, J. T. Yang, Lipid-induced ordered conformation of some peptide hormones and bioactive oligopeptides predominance of the helix over the beta-form. Biochemistry 1982, 21, 4556-4562. 

Fig. 3 Synthesis of homo- and copolymers with pendent bioactive oligopeptides by Ring Opening Metathesis Polymerization (ROMP). E = Glu (glutamic acid) [10]...

Twenty-three bioactive oligopeptides from 4 to 18 amino acids in size (e.g., leucokinin II, fibrinopeptide, angiotensin n, ACTH 1-10, neurostatin, tyr-somato-statin) were studied on a microbote C]g column (electrochemical detector at -fO.88 and 0.5 V vs. Ag/AgCI) and a complex 60-min 0/100 -> 60/40 acetonitrile/(3/97 IPA/water [0.1 % TEA]) gradient [1311]. The authors note that the IPA was present in... 

The chirality of DNA was applied to selective separation. A DNA aptamer as a new target-specific chiral selector for HPLC was investigated by Michaud et al. [119,120]. They showed that a tailor-made chiral stationary phase based on a DNA aptamer with known stereospecific binding for the D-enantiomer of the oligopeptide, arginine-vasopressin, exhibits enantioselectivity between the d- and L-peptides. This DNA-based target-specific aptamer chiral stationary phase provides a powerful tool for the resolution of small (bioactive) molecule enantiomers. 

Hydrolysis of peptides and proteins in the GI tract can occur luminally, at the brash border and intracellularly. Luminal activity from the pancreatic proteases trypsin, chymotrypsin, elastase and carboxypeptidase A is mainly directed against large dietary proteins. The main enzymatic activity against small bioactive peptides is derived from the bmsh border of the enterocyte. Brash border proteases, such as aminopeptidase A and N, diaminopeptidease IV and Zn-stable Asp-Lys peptidase, preferentially cleave oligopeptides of up to 10 ammo acid residues and are particularly effective in the cleavage of tri- and tetra-peptides. 

Peptide amphiphUes (PAs) are well known to form functirmal supramolecular materials [68]. PAs consists of (i) a short hydrophobic domain, often an alkyl chain, linked to (ii) an oligopeptide that induces and guides self-assembly by the formatiOTi of P-sheets, and (iii) an oligopeptide containing a bioactive domain [69]. In water, these molecules assemble into high-aspect-ratio nanofibers, which entangle and... 

Liquid crystalline phases are also of interest from the point of view of controlled or sustained release, or even the absence (e.g. in the case of certain potent enzymes) of such release of bioactive molecules. For example, due to the presence of both water and oil channels in bicontinuous cubic structures, such systems are capable of solubilizing both hydrophilic, hydrophobic and amphiphilic drugs, the release of which can be sustained over extended periods of time. Particularly interesting in this respect is the incorporation of large oligopeptide or macromolecular drugs (e.g. enzymes). For example, Ericsson et al. investigated the incorporation of lysozyme in a cubic phase formed by monoolein and water, and found that a considerable amount could be solubilized in the liquid crystalline phase (182). Furthermore, the incorporation of c -lactalbumin, bovine serum albumin and pepsin was found to resemble that... 

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