Bioactive peptides properties

The above examples illustrate the versatility and overlapping substrate specificities of peptidases, but they also serve to explain the difficulties faced by medicinal chemists who try to design bioactive peptides that have improved pharmacokinetic properties. Clearly, general predictive rules and a global understanding of the in vivo fate of peptides are not in sight, but the sections below will show that medicinal chemists have developed various successful strategies of a rather empirical nature [7][181-188],... 

The potential utility of peptides as therapeutic agents with clinical applications is limited as a consequence of intrinsic peptide properties such as metabolic instability or poor transmembrane mobility. Hence, the design and synthesis of meta-bolically stable peptide analogs that can either mimic or block the bioactivity of natural peptides or enzymes is an important area of medicinal chemistry research. Numerous structural modifications to peptides have been examined in pursuit of molecules with more desirable properties [1-3]. These modified structures, peptidomimetics, are nonpeptide molecules that imitate the desired properties of the natural substances. 

Modification of the properties of bioactive peptides incorporating constrained amino acids into the backbone structures has been explored in recent years. One of the best strategies to obtain good results in this area is to use an a,a-disubstimted amino acid, which has necessitated development of various methodologies to prepare these non-proteinogenic amino acids in enantiomerically pure form. " ... 

It is more difficult to prepare a chiral a,a-dialkylammo acid. Nevertheless, when such analogues are incorporated into the backbone of a peptide chain, analogues with modified properties are obtained. In this context, such residues have been evaluated as a new type of conformational constraint for the synthesis of enzyme-resistant agonists and antagonists of bioactive peptides. Here, the asymmetric synthesis or the resolution of the chiral quaternary amino acid is necessary and numerous procedures, which have recently been reviewed, were developed to produce the requisite amino acids in enantiomerically pure form. 

As antioxidant peptides are rarely present in marine invertebrates, they must be released from the parent protein by hydrolysis with enzymes. Various enzymes have been used to release peptides from muscle proteins. To date, different muscle proteins have been extracted, hydrolysed, and their antioxidant activities studied, which is among all invertebrate muscles the most similar to vertebrate skeletal muscle. Various studies have been conducted to investigate the antioxidant properties of hydrolysates or bioactive peptides from marine invertebrate sources like oysters... 

Because of their well-recognized physicochemical properties (relatively high hydrophobicity, cationic character, and short length) reversed-phase, size-exclusion, and cation exchange chromatographies are particularly appropriate to purify bioactive peptides from the immune system of invertebrates. The sensitivity of HPLC, MS, Edman degradation, and liquid growth inhibition assays allow one to use from narrow (e.g., 2.1-mm internal diameter) down to micro-or nano-columns. 

The protein fraction of milk is known to contain many valuable components and biologically active substances, which confer special properties for the support of infant development and growth (Meisel and Schlimme, 1990). Many milk-born bioactivities are latent, requiring proteolytic release of bioactive peptides from inactive native proteins (Schanbacher et al., 1998). Milk protein-derived bioactive peptides include a variety of substances that are potential modulators of various regulatory processes and reveal... 

Meisel, H. 1997. Biochemical properties of bioactive peptides derived from milk proteins potential nutraceuticals for food and pharmaceutical applications. Livestock Prod. Sci. 50, 125-138. 

A whey protein hydrolysate BioZate , containing ACE-inhibitory peptide was recently developed by Davisco Foods International Inc. The effect on blood pressure was studied with 30 unmedicated, non-smoking, borderline hypertensive men and women, and daily dose was 20 g. The results indicated that there was a significant drop in both systolic and diastolic blood pressure after 1-week treatment, which persisted throughout the study of 6 weeks. The application of this product is varied and flexible. In addition to the bioactive peptides, it has functional properties such as emulsification and foaming (Klink, 2002). 

Ingredia, a French dairy company, has developed Prodiet F 200 , a milk protein hydrolysate that contains a bioactive peptide with relaxing properties. The patented product has an anti-stress effect proven by several clinical studies and does not cause the classical side effects of anxiolytics. Food supplements, chocolate and animal feed are examples of its applications (Lefranc, 2002). 

Nowadays, several solution structures of membrane-bound peptides and protein fragments have been reported (33,34). More important is that bicelles have been used successfully to investigate the effect of bioactive peptides on lipid properties, such as order and dynamics, and at the same time of the dynamics of the peptides themselves (35,36). 

Food materials, including fish, contain the precursors to these bioactive peptides, which can be formed in vitro or in vivo by enzymatic hydrolysis (Korhonen and Pihlanto 2003). During the past decade, a number of studies have reported on the many physiological properties of these bioactive peptides. The aim of this review is to describe the production of novel peptides derived from marine protein hydrolysates, elucidating the underlying mechanisms of physiological and biofunctional activity that are particular to individual bioactive peptides. The general sources and production of protein hydrolysates will be discussed, followed by a discussion of the nutraceutical properties of protein hydrolysates and their associated bioactive peptides. 

PHYSIOLOGICAL PROPERTIES OF PROTEIN HYDROLYSATES AND ASSOCIATED BIOACTIVE PEPTIDES... 

Besides ACE-inhibitory and antioxidative activities, other biological properties have been reported for protein hydrolysates and their associated bioactive peptides. For example, earlier studies demonstrated a hypolipidemic effect of fish protein (Bergeron and Jacques, 1989 Zhang and Beynen, 1993). A recent study by Tanaka et al. (2006) demonstrated production of protein hydrolysates from oyster prepared with aloase, an endoprotease from Bacillus subtilis, and... 

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