Peptides uncommon amino acids

It consists of a chromogenic group which bears two identical, cyclic pentapeptide components. Several actinomycins are known they differ from each other in their peptide components. As is often the case with physiologically active peptides, uncommon amino acids e.g. sarcosine, are found as structural components. The occurrence of uncommon components and their cyclization to a ring structure protect the physiologically... 

A Caribbean cyanobacterium Hormothamnion enteromorphoides was found to produce a complex mixture of cytotoxic and ichthyotoxic peptides, hormothamnins, which may explain the apparent absence of predation on these potentially palatable life forms. Initial chemical characterization suggested that the major peptide, hormothamnin A, is a cyclic undecapeptide containing six common and five uncommon amino acid residues (320). 

Amino acid analysis can be performed for detecting all the amino acids or for few specific ones. Regardless of the type of method, analysis of amino acids is a difficult task because the majority of the amino acids lack a strong chromophore and they resemble each other in structure, which makes the separation very difficult. Thus, they need extra reaction steps to be derivatized pre- or postseparation. Furthermore, physiological fluids like serum contain many interfering compounds such as peptides and the uncommon amino acids. Amino acid analysis can be requested for a wide variety of purposes such as clinical (diagnostic), nutritional, or for basic structure determination. 

Quantification of free amino acids in serum, urine, or other physiological fluids The separation here is complicated by the presence of many interfering substances, such as small peptides and uncommon amino acids. This analysis is requested often for screening purposes. 

The cyclic 11-peptide contains mainly normal amino acids, one D-alanine and one L-a-aminobutyric acid, but, strikingly, not less than seven iV-methyl groups and a quite uncommon amino acid, a C9-compound (4R)-4[(F)-2-butenyl]-4-methyl-N-methyl-L-threonine. 

In Stuttgart, Ulrich Schmidt with his associates have synthesized numerous cyclopeptides containing uncommon amino acids from plants (peptide alkaloids) and from moulds, (ansacyclopeptides with diphenylether units). 

Microorganisms and plants can synthesize many uncommon amino acids. For example, some microbes make 2-aminoisobutyric acid and lanthionine, which is a sulfide-bridged derivative of alanine. Both of these amino acids are found in peptidic lantibiotics such as alamethicin. While in plants, 1-aminocyclopropane-l-carboxylic acid is a small disubstituted cyclic amino acid that is a key intermediate in the production of the plant hormone ethylene. 

Uncommon Amino Acids Found in Naturally Occurring Peptides... 

Some naturally occurring peptides, as we have said previously, contain certain uncommon amino acids. It should be noted here that the... 

The dual presence, of linkages other than the classical a-peptide bond, and of uncommon amino acids in numerous naturally occurring peptides, enables us to predict that, if enzymes exist which hydrolyze such peptides, these enzymes should differ by their specificity from the peptidases which hydrolyze peptides resulting from the partial degradation of proteins. Actually, the supposition is true, for several such enzymes are known, which we shall at least mention in this review. 

The problem of N-terminal variants in recombinant proteins is not uncommon. E. coli synthesizes proteins with a formylated methionine at the N terminus. In vivo, E. coli often removes N-formyl methionine with the action of a deformylase followed by methionine amino peptidase. This removal is not always exact and neighboring amino acids in the peptide chain influence the removal.130 This can yield recombinant products lacking a number of encoded amino acids at the N terminus. For smaller proteins, these product-related impurities generally are detected and quantitated by RP-HPLC. However, large proteins differing by only one or two N-terminal amino acids may be difficult to resolve by RP-HPLC. In these instances, peptide mapping by RP-HPLC is a valuable tool. 

Among peptide libraries today, such NP-complete sets are uncommon. It is often profitable to expand the monomer set to include unnatmal amino acids, thus once again leading to infinite possibilities. Even within the narrower context of natural peptides, the complete set of 20 amino acids is seldom employed in synthetic libraries. In Houghten s example above, both cysteine and tryptophan were omitted to avoid problems due to oxidative side reactions, while others often substitute... 

Interestingly, a series of homo-peptides derived from the C -didehydro a-amino acid with the shortest side chain (C -didehydroalanine or AAla, 6) was shown unambiguously to overwhelmingly adopt a multiple, consecutive, fully extended conformation (29). These peptide molecules are essentially flat, including the amino acid side chains, and form completely planar sheets (Fig. 5). This uncommon peptide 3-D structure is stabilized by two types of intramolecular H-bonds, Nj-H- Oi=Ci (typical of the 2.05-helix) and Oi=Ci (characteris-... 

Hietter, H, Schultz, M, Kunz, H, Solid-phase synthesis of a 36 amino acid O-fucosyl-peptide with the uncommon Thr-Fuc linkage, Synlett, 1219-1220, 1995. 

The methods employed to deduce the structures of peptides have been reviewed by several authors and are not commented on here. These methods, when applied to peptides of animal origin with their limited number of amino acids, can be used with a minimum amount of peptide and the released amino acids or their reaction products can usually be identified unequivocally by chromatographic procedures. In the case of peptide antibiotics with their many uncommon constituents, the characterization of these components is an additional task. Even the amino acids themselves need a careful investigation. They may be derivatives of common amino acids, they may be secondary degradation products from unusual components, or they may have D-configuration. Therefore the components have usually to be isolated in amounts which allow a careful chemical and physicochemical characterization, and often direct comparison with synthetic compounds is necessary. 

On-resin lactam (amide) formation or cyclization can be achieved via HOBt active esters using a number of reagents. Carbodiimide and phosphonium activation have all been used for ring closure with minimal loss of chiral integrity of the activated amino acid residue. The choice of reagent and auxiliary nucleophile (i.e. HOBt, HOAt) is at the discretion of the operator (see Chapters 2 and 3). However, it is worth noting that successful peptide cyclization is, to an extent, sequence dependent. Nominal ring closure is not uncommon and is due in part to the spatial orientation of the peptide backbone and steric hindrance. 

---