Glutamic acid peptides

HE Klieger. On peptide synthesis I. Synthesis of glutamic acid peptides using car-bobenzoxy-L-pyroglutamic acid. Justus Liebig s Ann Chem 640, 145, 1961. 

Poly-L-glutamic acid Peptide absorption spectrum from 1900-2400 A is conformation-dependent Imahori and T anaka (1959)... 

Poly-L-lysine and poly-L-glutamic acid Peptide absorption peak split for a-helical form sharp transition at pH 9 forpoly-Lys (random helical) Tinoco et al. (1961)... 

Fig. 12. Tryptic map of it-PA (mol wt = 66,000) showing peptides formed from hydrolysis of reduced, alkylated rt-PA. Separation by reversed-phase octadecyl (C g) column using aqueous acetonitrile with an added acidic agent to the mobile phase. Arrows show the difference between A, normal, and B, mutant rt-PA where the glutamic acid residue, D, has replaced the normal arginine residue, C, at position 275.

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. 

The Dmab group was developed for glutamic acid protection during Fmoc/r-Bu based peptide synthesis. The group shows excellent acid stability and stability toward 20% piperidine in DMF. It is formed from the alcohol using the DCC protocol for ester formation and is cleaved with 2% hydrazine in DMF at rt. ... 

It is a peptide containing 27 amino acid residues containing the amino acids L-histidine (His) L-aspartic acid (Asp) L-serine (Ser) glycine (Gly) L-threonine (Thr) L-phenyl-alanine (Phe) L-glutamic acid (Glu) L-glutamine [Glu(NHj)] L-leucine (Leu) L-arginine (Arg) L-alanine (Ala) and L-valinamide (Va -NHj). 

Since the proline residue in peptides facilitates the cyclization, 3 sublibraries each containing 324 compounds were prepared with proline in each randomized position. Resolutions of 1.05 and 2.06 were observed for the CE separation of racemic DNP-glutamic acid using peptides with proline located on the first and second random position, while the peptide mixture with proline preceding the (i-alamine residue did not exhibit any enantioselectivity. Since the c(Arg-Lys-0-Pro-0-(i-Ala) library afforded the best separation, the next deconvolution was aimed at defining the best amino acid at position 3. A rigorous deconvolution process would have required the preparation of 18 libraries with each amino acid residue at this position. 

The improvements in resolution achieved in each deconvolution step are shown in Figure 3-3. While the initial library could only afford a modest separation of DNB-glutamic acid, the library with proline in position 4 also separated DNP derivatives of alanine and aspartic acid, and further improvement in both resolution and the number of separable racemates was observed for peptides with hydrophobic amino acid residues in position 3. However, the most dramatic improvement and best selectivity were found for c(Arg-Lys-Tyr-Pro-Tyr-(3-Ala) (Scheme 3-2a) with the tyrosine residue at position 5 with a resolution factor as high as 28 observed for the separation of DNP-glutamic acid enantiomers. 

Figure 11a shows a force-distance profile measnred for poly(L-glutamic acid) brushes (2C18PLGA(44)) in water (pH = 3.0, 10 M HNO3) deposited at 40 mN/m from the water subphase at pH = 3.0. The majority of peptides are in the forms of an a-helix (38% determined from the amide I band) and a random coil. Two major regions are clearly seen in... 

Nodularia spwnigena has also been shown to produce a peptide with hepato-toxic activity. The more recent reports come from Australia (76), the German Democratic Republic (77), Denmark (78), Sweden (79), and Finland (80,81). Recently structure information on Nodularia toxin has been presented by Rinehart (97) for waterbloom material collected in Lake Forsythe, New Zealand, in 1984 by Eriksson et al. (81) from waterbloom material collected in the Baltic Sea in 1986, and Runnegar et al. (82) for a field isolate from the Peel Inlet, Perth, Australia. Structure work by Rinehart, Eriksson, and Runnegar all indicate that the peptide is smaller than the heptapeptide toxins. Rinehart s work (97) indicates the toxin is a pentapeptide with a similar structure to the heptapeptides and containing fi-methylaspartic acid, glutamic acid, arginine, dehydrobutyrine, and ADDA (MW 824). 

Sidechain conservatism may be split up into at least two kinds 1) substitutions which conserve sidechain bonding forces - providing similar electrostatic, hydrophilic, or hydrogen bonding interactions, and 2) substitutions conserving secondary structure propensity. For instance, substitution of glutamic acid with aspartic acid conserves charge, but this could have a considerable effect upon the secondary structure propensity of the peptide. 

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