Proteins protected peptides

However, interpretation of, or even obtaining, the mass spectrum of a peptide can be difficult, and many techniques have been introduced to overcome such difficulties. These techniques include modifying the side chains in the peptide and protecting the N- and C-terminals by special groups. Despite many advances made by these approaches, it is not always easy to read the sequence from the mass spectrum because some amide bond cleavages are less easy than others and give little information. To overcome this problem, tandem mass spectrometry has been applied to this dry approach to peptide sequencing with considerable success. Further, electrospray ionization has been used to determine the molecular masses of proteins and peptides with unprecedented accuracy. 

Although equal amounts of the two possible forms are generated in every synthesis of amino acids, (almost) only L-amino acids are incorporated into proteins and peptides. This phenomenon is valid for the amino acids in all life forms, from the bacterium to the elephant. But there are exceptions some antibiotics contain D-amino acids in their proteins, and these also occur in a few components of cell walls. Here, the D-amino acids have a certain protecting function with respect to degradation enzymes, which are specialised to deal with L-amino acids. 

Some reports even indicate that the conjugation of proteins or peptides with carbohydrates can increase dramatically their activity compared to that of the native state (Susaki et al., 1998). Carbohydrates also can provide a protective effect on modified peptides toward proteolytic digestion (Rudd et al., 1994) or mask recognition of a peptide by the immune system (Harding et al., 1993). The creation of neoglycoproteins thus can affect the activity of peptides and proteins, which are not normally glycosylated in vivo. 

Schulze, K., Olive, C., Ebensen, T., and Guzman, C. A. (2006). Intranasal vaccination with Sfbl or M protein-derived peptides conjugated to diphtheria toxoid confers protective immunity against a lethal challenge with Streptococcus pyogenes. Vaccine 24, 6088-6095. 

High temperatures can break native S-S bonds and form new S-S bonds which can lock the protein into a denatured eonfiguration [89]. Low pH, sodium dodecyl sulfate. Tween 80, chaotropie salts, and exogenous proteins have been used to protect proteins from thermal inaetivation [90]. Ethylene glycol at 30-50% was used to protect the antiviral activity of P-interferon preparations [91]. Human serum albumin was used in recombinant human interferon-Psei-n which resulted in increased thermal stability [62]. Water-soluble polysaeeharides sueh as dextrans and amylose [92], as well as point-specific (site-directed) mutagenesis [93] have also been used to increase thermal stability of therapeutie proteins and peptides. 

A novel concept of using bioadhesive polymers as enzyme inhibitors has been developed [97]. Included are derivatives of poly acrylic acid, polycarbophil, and car-bomer to protect therapeutically important proteins and peptides from proteolytic activity of enzymes, endopeptidases (trypsin and a-chymotrypsin), exopeptidases (carboxypeptidases A and B), and microsomal and cytosolic leucine aminopeptidase. However, cysteine protease (pyroglutamyl aminopeptidase) is not inhibited by polycarbophil and carbomer [97]. 

Hydrophilic polymers are currently undergoing investigation for improving the transport of biomacromolecules across the intestinal walls. Hydrophilic polymers have been shown to protect proteins and peptides from proteolysis. Multiple methods utilize the properties of polymers to protect biomacromolecules without removing them from the aqueous environment of the intestines. 

Polymers that are protease inhibitors and polymer-inhibitor conjugates are now widely investigated for their ability to protect proteins and peptides from proteolytic degradation. These molecules are effective in the immediate area surrounding the delivery device, so the effects on proteins that have diffused far from the delivery device are limited. Due to the fact that bioadhesives were used as the conjugating polymer, the delivery device may adhere to the intestinal lining. If this does happen, the diffusional distance of the protein from the device to the intestinal wall will be quite short. One barrier that the protease inhibitors do not affect is the cellular barrier. Biomacromolecules must still find a method to enter the cells or be taken up by phagocytosis. 

The use of polymers to deliver protein and peptides has had some success. Most of these systems have been based on encapsulating the protein or peptide within a polymer. The protection that the polymer gives the peptide from proteolysis was the... 

With all of the advances in polymer science and conjugation technology, many methods have been developed to increase the feasibility of oral peptide and protein delivery. There is still no single mechanism that can be used to protect a protein or peptide from degradation and increasing oral availability, but with the multitude of new methods for allowing a protein to negotiate natural barriers, oral delivery of any systemically active protein is a definite possibility at some point in the future. 

Calabrese Y, Calvani M, Butterfield DA. 2006d. Acetyl-L-camitine-induced up-regulation of heat shock proteins protects cortical neurons against amyloid-beta peptide 1-42-mediated oxidative stress and neurotoxicity Implications for Alzheimer s disease. 

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