Peptides, antibiotic amino acids

Cycioheptamycin - peptide antibiotic Amino acid is toxic and teratogenic... 

Amberlite IRC-50 3.5 1.25 Methacrylic acid-DVB. Selectivity adsorbs organic gases such as antibiotics, alkaloids, peptides, and amino acids. Use pH >5. 

Three approaches can be employed to separate peptide stereoisomers and amino acid enantiomers separations on chiral columns, separations on achiral stationary phases with mobile phases containing chiral selectors, and precolumn derivatization with chiral agents [111]. Cyclodextrins are most often used for the preparation of chiral columns and as chiral selectors in mobile phases. Macrocyclic antibiotics have also been used as chiral selectors [126]. Very recently, Ilsz et al. [127] reviewed HPLC separation of small peptides and amino acids on macrocyclic antibiotic-based chiral stationary phases. 

A few other biologically interesting and naturally occurring peptides and amino acids of rather simple structure were synthesized using the Ugi four-component reaction (Figure 12.5) the phosphonic acid antibiotics plumbemycin A 249 and B 250 [126], both epimers of the polychlorinated antihypertensive peptide (+)-demethyldysidenin 251 [127], and the nucleoside antibiotic nikkomycin 252 [128]. 

The prevalence of the carboxylate moiety in both biogenic and man-made molecules of interest makes this functional group a popular target for anion host chemistry. Needless to say, carboxylates are a major constituent of proteins, peptides and amino acids, and the expansion of proteomics begets increasing requirements for means of specific detection of such biomolecules. Other relevant examples of carboxylates include fatty acids, while many small molecule di- and tricarboxylates are implicated in key metaboUc pathways such as the citric acid cycle (e.g. citrate, succinate, fumarate and malonate). Carboxylated anthropogenic molecules include trichloroacetic acids, anionic surfactants and S-lactam antibiotics. 

Thiostrepton family members are biosynthesized by extensive modification of simple peptides. Thus, from amino acid iacorporation studies, the somewhat smaller (mol wt 1200) nosiheptide, which contains five thiazole rings, a trisubstituted iadole, and a trisubstituted pyridine, is speculated to arise from a simple dodecapeptide. This work shows that the thiazole moieties arise from the condensation of serine with cysteiae (159,160). Only a few reports on the biosynthesis of the thiostrepton family are available (159,160). Thiostrepton is presently used ia the United States only as a poly antimicrobial vetetinary ointment (Panalog, Squibb), but thiazole antibiotics have, ia the past, been used as feed additives ia various parts of the world. General (158) and mechanism of action (152) reviews on thiostrepton are available. 

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 10.35 The amino acid sequences of several amphipathic peptide antibiotics, a-Helices formed from these peptides cluster polar residues on one face of the helix, with nonpolar residues at other positions. 

Depicted in Fig. 2, microemulsion-based liquid liquid extraction (LLE) of biomolecules consists of the contacting of a biomolecule-containing aqueous solution with a surfactant-containing lipophilic phase. Upon contact, some of the water and biomolecules will transfer to the organic phase, depending on the phase equilibrium position, resulting in a biphasic Winsor II system (w/o-ME phase in equilibrium with an excess aqueous phase). Besides serving as a means to solubilize biomolecules in w/o-MEs, LLE has been frequently used to isolate and separate amino acids, peptides and proteins [4, and references therein]. In addition, LLE has recently been employed to isolate vitamins, antibiotics, and nucleotides [6,19,40,77-79]. Industrially relevant applications of LLE are listed in Table 2 [14,15,20,80-90]. 

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. 

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