Amino acid derived peptides

Ring Opening by Nitrogen Nucleophiles fl-Amino Amides and fi-Amino Acid-Derived Peptides... 

From the ring opening of p-lactams by amines and a-amino acids, p-amino amides and fi-amino acid derived peptides are generated. These structures are of interest because of their presence in several naturally occurring macrocyclic compounds [82, 83]. One example of the latter is the p-hydroxy aspartic acid derived tripeptide 45 found in the macrocyclic peptide lactone antibiotic lysobactin 40 [84], Fig. 4. 

The palladium catalyzed hydrogenolysis of 3-amino 4-aryl azetidin-2-ones, Fig. 11, constitutes an excellent and reliable strategy to access a-amino acid derived peptides. The discovery, development, and synthetic opportunities of this approach have been reviewed by Ojima [145-148], and will not be covered here. Only the... 

Th. Wieland, Ch. Birr, Some experiments with resin-activated amino acid derivatives. Peptides 1966, Proc. 8th Eur. Peptide Symp. (North-Holland Publ. Company Amsterdam 1967) pp. 103-106. See here references to the parallel attempts of M. Fridkin, A. Patchornik, E. Katchalski. 

Attachment of chiral substituents to calixarene skeleton is the first, the most straightforward and still the most popular way to constmct chiral calixarenes. In 1979 Gutsche reported the synthesis of the first chiral calixarene by attaching camphorosulfonyl group to p-tBu-calix[8]arene [1]. Nowadays, attachment of virtually any chiral moiety at the selected position is synthetically feasible. However, some chiral groups, due to their availability and versatility, have been particularly widely exploited, for example amino acid derivatives, peptides, carbohydrates, chiral amines and axially chiral groups. 

Derivatives such as 3-fluoro-4-nitropyridine [13505-01 -6] (396) or the 1-oxide [769-54-0] (397) have been used to characteri2e amino acids and peptides. 5-Eluoro-3-pyridinemethanol [22620-32-2] has been patented as an antihpolytic agent (398). A promising antidepressant, l-(3-fluoro-2-pyridyl)pipera2ine hydrochloride [85386-84-1] is based on 2-chloro-3-fluoropyridine [17282-04-1] (399). 

Mass spectral fragmentation patterns of alkyl and phenyl hydantoins have been investigated by means of labeling techniques (28—30), and similar studies have also been carried out for thiohydantoins (31,32). In all cases, breakdown of the hydantoin ring occurs by a-ftssion at C-4 with concomitant loss of carbon monoxide and an isocyanate molecule. In the case of aryl derivatives, the ease of formation of Ar—NCO is related to the electronic properties of the aryl ring substituents (33). Mass spectrometry has been used for identification of the phenylthiohydantoin derivatives formed from amino acids during peptide sequence determination by the Edman method (34). 

However, the use of a HPLC separation step enabled a remarkable acceleration of the deconvolution process. Instead of preparing all of the sublibraries, the c(Arg-Lys-O-Pro-O-P-Ala) library was fractionated on a semipreparative HPLC column and three fractions as shown in Fig. 3-2 were collected and subjected to amino acid analysis. According to the analysis, the least hydrophobic fraction, which eluted first, did not contain peptides that included valine, methionine, isoleucine, leucine, tyrosine, and phenylalanine residues and also did not exhibit any separation ability for the tested racemic amino acid derivatives (Table 3-1). 

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. ... 

Applications of the oxalate-hydrogen peroxide chemiluminescence-based and fluorescence-based assays with NDA/CN derivatives to the analysis of amino acids and peptides are included. The sensitivity of the chemiluminescence and fluorescence methods is compared for several analytes. In general, peroxyoxalate chemiluminescence-based methods are 10 to 100 times more sensitive than their fluorescence-based counterparts. The chief limitation of chemiluminescence is that chemical excitation of the fluorophore apparently depends on its structure and oxidation potential. 

A nomenclature was proposed by Seebach for the description of / -amino acids according to their substitution pattern, and for naming the resulting / -peptides [66, 67]. Enantiomerically pure / -amino acid derivatives with substituents in the 2-or 3-position are thus defined as - and / -amino acids, respectively (abbreviated to H-/ -HXaa-OH and H-/ -HXaa-OH). The corresponding /S-peptides built from these monomers will be named ff - and / -peptides. Similarly, /S -peptides consist of / -amino acid residues with substituents in both the 2- and 3-positions. Finally, peptides built from geminally disubsituted amino acids are referred to as and / -peptides (Fig. 2.6). 

These studies conducted in solution and in the solid state revealed a common 3i4-helical fold stabilized by H-bonds closing 14-membered rings formed between NH and C=0 +2 (see Fig. 2.12A and C). It is noteworthy that the 3i4-helix of j -peptides with L-amino acid-derived chirality centers (Fig. 2.12 A) and the a-helix have opposite polarity and helicity. 

Peptides built from y-amino acids with L-amino acid-derived chirahty centers form a right-handed (P)-2.6i4 hehx of ca. 5 A pitch with both ethane bonds in a -y)-synclinal conformation (mean values for dihedral angles 9 and 82 of central residues 2-5 in compounds 141 are 72.5 and 64.3°, respectively Fig. 2.36 A and B Tab. 2.8). 

In mammals, peptide hormones typically contain only the a-amino acids of proteins finked by standard peptide bonds. Other peptides may, however, contain nonprotein amino acids, derivatives of the protein amino acids, or amino acids finked by an atypical peptide bond. For example, the amino terminal glutamate of glutathione, which participates in protein folding and in the metabolism of xenobiotics (Chapter 53), is finked to cysteine by a non-a peptide bond (Figure 3—3). The amino terminal glutamate of thyrotropin-... 

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. 

Zhao, Q., Sannier, F., Garreau, I., Lecoeur, C., and Piot, J. M., Reversed-phase high-performance liquid chromatography coupled with second-order derivative spectroscopy for the quantitation of aromatic amino acids in peptides application to hemorphins, /. Chromatogr. A, 723, 35, 1996. 

Amino Acids and Peptides Carbohydrate Chemistry Parti Mono-, Di-, and Trisaccharides and Their Derivatives... 

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