Peptides and peptide derivatives

In conclusion, the BAL method is a novel and general strategy for solid-phase synthesis of peptides and peptide derivatives, is compatible with a wide range of functionalized polymeric supports, and is readily generalizable to other nitrogen-containing molecules.9... 

SUPRAMOLECULAR POLYMERIZATION OF PEPTIDES AND PEPTIDE DERIVATIVES NANOFIBROUS MATERIALS... 

This chapter commences with Section 7.1 which deals with reversed-phase chromatography (RPC) and related techniques as applied to synthetic peptides 1-3 A detailed discussion on RPC is presented. Basic considerations are covered as are issues of fundamental physical chemistry. Many examples of chromatography and quantitative relationships are described for peptides and peptide derivatives. There is also an extensive table of naturally occurring peptides that have been isolated and purified by RPC techniques. The section includes many examples of RPC and HPLC profiles of peptidic systems. 

Table 6. ACE inhibition by plant peptides and peptides derived from plant protein proteolysis...

When optically active amino acids are released from peptides by aminopeptidase, they must be of the L-configuration. For this reason, complete hydrolysis of synthetic polypeptides with aminopeptidase provides a convenient means for evaluating the sterochemical homogeneity of synthetic peptides and peptide derivatives (Hofmann et al, 1962). 

Table 6. ACE inhibition by plant peptides and peptides derived from plant protein proteolysis Peptide sequences are given in both the three-letter and one-letter codes. Triticum aestivum (wheatgerm) protein was proteolysed by Bacilllus lichenoformis alkaline protease [i99] and Zea mays (com seed) a-zein was proteolysed by thermolysin [203, 204],...

This chapter will introduce polymer systems containing either naturally occurring maaomolecules (polysaccharides, proteins, DNA) or their subunits (bioanalogous molecules, amino acids, short peptides and peptide derivatives, polypeptides, polynucleotides), respectively. The natural building blocks can be connected by covalent bonds or by self-assembly and either can be used alone (see, e.g.. Section 5.4) or in combination with synthetic polymer units (biohybrids). Alternatively the building block itself may be a hybrid of a natural and synthetic molecule (bioconjugate cf. Section 3.5), as, for instance, a PEG-peptide conjugate. 

The development by Bergmann and Zervas (22) of a practical method for the synthesis of a wide variety of peptides and peptide derivatives was followed by extensive studies of the specificity of papain. Hippurylamide was one of the early synthetic substrates found to be rapidly split by papain (23). Later it was found that benzoyl-L-isoglutamine was even more rapidly hydrolyzed (21), and finally Bergmann and Fruton (18) demonstrated that a-benzoyl-L-argininamide (BAA) appeared to be the most sensitive substrate of all. In this sense, papain appeared to resemble trypsin in its specificity since BAA was also the best substrate for this enzyme. However, after investigation of over 65 peptides and peptide derivatives (19-25), it became apparent that the specificity of papain was not nearly so limited as that of trypsin. Bergmann and Fruton (20) pointed out that papain hydrolyzed peptides derived from a wide... 

Folic acid and its derivatives (mostly the tri-and heptaglutamyl peptides) are widespread in nature. It is a specific growth ctor for certain micro-organisms, but in animals the intestinal bacteria provide the small quantities needed for growth. The coenzyme forms are actually... 

The /-butoxycarbonyl group (Boc, "t-box ) has been eMens vely used in peptide synthesis, and Boc derivatives of many amino acids are commercially available. The customary reagent for the preparation from the amine is t-butyl azidoformate in water, dioxane/water, DMSO, or DMF. The cleavage by acids of medium strength proceeds with concomitant loss of isobutene and carbon dioxide (L.A. Carpino, 1957, 1973 see section 4.1.2.2). 

Certain amino acids and their derivatives, although not found in proteins, nonetheless are biochemically important. A few of the more notable examples are shown in Figure 4.5. y-Aminobutyric acid, or GABA, is produced by the decarboxylation of glutamic acid and is a potent neurotransmitter. Histamine, which is synthesized by decarboxylation of histidine, and serotonin, which is derived from tryptophan, similarly function as neurotransmitters and regulators. /3-Alanine is found in nature in the peptides carnosine and anserine and is a component of pantothenic acid (a vitamin), which is a part of coenzyme A. Epinephrine (also known as adrenaline), derived from tyrosine, is an important hormone. Penicillamine is a constituent of the penicillin antibiotics. Ornithine, betaine, homocysteine, and homoserine are important metabolic intermediates. Citrulline is the immediate precursor of arginine. 

FIGURE 5.20 Trypsin is a proteolytic enzyme, or protease, that specifically cleaves only those peptide bonds in which arginine or lysine contributes the carbonyl function. The products of the reaction are a mixture of peptide fragments with C-terminal Arg or Lys residues and a single peptide derived from the polypeptide s C-terminal end. 

Lipase M (Mucor javanicus), pH 7, 37°, 70-88% yield. In this case, a- and )3-glycosidic peptide derivatives were deprotected. Acetates on the pyrano-sides were not affected. ... 

The study of the / -thienylalanines and of peptides derived from them as antimetabolites has been continued. - " ... 

A very considerable body of work has been published on the use of 3-hydrox-ytriazolopyridine (HOAt) 280 and its derivatives as peptide coupling catalysts,... 

Many low weight compounds produced by microor-ganism-like formylated peptides as well as endogenous mediators are chemotactic for leukocytes and promote the inflammatory process. The main endogenous compounds are listed in Table 1 and are derived from activated plasma protein cascades that function as amplification mechanisms, are performed and released from activated cells or are de novo synthesized on demand by cells participating in or being affected by inflammatory events. The major modulators of leukocyte adhesion to endothelial cells are listed in Table 2. 

Besides sensitive methods for the analysis of proteins, bioinformatics is one of the key components of proteome research. This includes software to monitor and quantify the separation of complex samples, e.g., to analyze 2DE images. Web-based database search engines are available to compare experimentally measured peptide masses or sequence ions of protein digests with theoretical values of peptides derived from protein sequences. Websites for database searching with mass spectrometric data may be found at http //www.expasy.ch/tools, http //prospector.ucsf. edu/ and http //www.matrixscience.com. 

The method illustrated here does have, however, several excellent features.10 The peptide yields are very good even in the synthesis of asparaginyl and glutaminyl peptides, which are ordinarily very difficult to prepare in reasonable yield. Furthermore, the by-products are all water-soluble and, therefore, easily removed from the product peptide derivative. One recrystallization, even under conditions of almost... 

The most widely studied interactions between biologically active ligands and organotin(lV) cations relate to the amino acids and their derivatives (N- or S-protected amino acids and peptides), though new data on several of the most commonly occurring amino acids are still being published. This is specially true for aqueous speciation studies. Nice and very detailed reviews were published in this area by Molloy and Nath. ... 

Figure 5.19 MALDI-ToF mass spectrum, providing a molecular-weight profile of the tryptic peptides derived from spot 22 (see Figure 5.18) of the silver-stained two-dimensional gel of the proteins extracted from the yeast S. cerevisiae. From Poutanen, M., Salusjarvi, L., Ruohonen, L., Penttila, M. and KaUddnen, N., Rapid Commun. Mass Spectrom., 15, 1685-1692, copyright 2001. John Wiley Sons Limited. Reproduced with permission.

The magaiitins are a class of hnear, cationic, faciaUy amphipathic and hehcal antibacterial peptides derived from frog skin [51]. The magaiitins exhibit highly selective and potent antimicrobial activity against a broad spectrum of organisms [52, 53]. As these peptides are faciaUy amphipathic, the magainins have a cationic heli-... 

Interestingly, the 28-hehcal fold identified by NMR analysis of /9-peptide 109 compares well with the model of a /9 -peptide consisting of 1-aminomethylcyclo-propanecarboxylic acid residues (Fig. 2.24). This model was generated using ideal torsion angle values ( = + 120°, 9i=-72°, ii/=0°, and < =180°) derived from crystal structures of dimer 110, trimer 111 and tetramer 112 [163] (Fig. 2.25). 

Lyim and co-workers carried out smdies of the Ap(io 35) peptide - derived from residues 10-35 of the p-amyloid responsible for Alzheimer s disease - which forms fibrils composed of parallel p-sheets [62]. The peptide was compared to its C-terminal PEG-derivatised analogue. TEM experiments showed that both formed fibrils [63] (Fig. 21) but the uranyl acetate stain was not found inside the peptide-PEG fibrils, indicating that PEG was at the outer edge of the fibril. 

Peptides are named for the number of amino acid residues present, and as derivatives of the carboxyl terminal residue. The primary structure of a peptide is its amino acid sequence, starting from the amino-terminal residue. 

A new chapter on amino acids and peptides, which emphasizes the manner in which the properties of biologic peptides derive from the individual amino acids of which they are comprised. 

Perhaps most importantly, MOP agonists can potentiate HIV propagation in lymphocytes, monocytes, and monocyte-derived macrophages/microglia (Peterson et al. 1990 Carr and Serou 1995). This includes morphine (Peterson et al. 1990, 1999, 2004 Hu et al. 2005), methadone (Douglas 2001), and the MOP peptide agonist endomorphin (Peterson et al. 1999). The effects of morphine on HIV... 

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