Dehydro peptides

Figure 4 The biosynthesis of nisin A as a representative example of the posttranslational maturation process of lantibiotics. Following ribosomal synthesis, NisB dehydrates serine and threonine residues in the structural region of the prepeptide NisA. NisC subsequently catalyzes intramolecular addition of cysteine residues onto the dehydro amino acids in a stereo- and regioselective manner. Subsequent transport of the final product across the cell membrane by NisT and proteolytic cleavage of the leader sequence by NisP produces the mature lantibiotic. For the sequence of the leader peptide, see Figure 6. Adapted with permission from J. M. Willey W. A. van der Donk, Annu. Rev. Microbiol. 2007, 61, 477-501.

The main genera responsible for freshwater toxic blooms are Microcystis, Anabaena, Aphanizomenon and Oscillatoria. Toxins produced include 1. anatoxins, alkaloids and peptides of Anabaena 2. the peptide microcystin and related peptides of Microcystis 3. aphantoxins, compounds of Aphanizomenon with properties similar to some paralytic shellfish poisons. Properties of Oscillatoria toxin suggest they are peptides similar to those of Microcystis. Microcystis toxins are peptides (M.W. approx. 1200) which contain three invariant D-amino acids, alanine, erythro-3-methyl aspartic and glutamic acids, two variant L-amino acids, N-methyl dehydro alanine and a 3-amino acid. Individual toxic strains have one or more multiples of this peptide toxin. The one anatoxin characterized is a bicylic secondary amine called anatoxin-a (M.W. 165). The aphantoxin isolated in our laboratory contains two main toxic fractions. On TLC and HPLC the fractions have the same characteristics as saxitoxin and neosaxitoxin. 

C.H. Stammer, Dehydro and cyclopropyl amino acids and peptides, NIDA Res. Monogr. 69, 148 (1986). 

The first family is represented by peptides based on a, 3-dehydro a-amino adds in which a C=C bond confers rigidity and electronic Y-conjugation on the system (Section 11.1). Peptides rich in these amino acids are widespread in nature, particularly as antibiotics, and possess interesting conformational properties. 1-11 In addition to the E and Z configurational isomers, occurring when two different atoms (substituents) on CP are present, fully-extended, characteristically flat conformations or p-tums and 310/a-helices may be induced by u,p-dehydro a-amino acids. 

In most cases of formation of peptides containing d-amino acid, the L form of the amino acid is the substrate for the incorporating enzyme. In contrast, the free D-amino acid is ordinarily a poor substrate for the incorporation reaction. Whether the racemization occurs on the enzyme or afterwards remains to be determined in most cases. In the case of the D-valyl residue formed in penicillin, a tripeptide derivative containing L-valine is an intermediate, and the conversion is thought to occur by way of an a,/3-dehydro form of the valyl residue. 

Oligomeric pyruvat-dehydro-genase-complex (PDC), promutagenes DNA base adduct 0(6)-Methylguanosin, 0(6)-Methylguanin-DNA Methyltransferase (MGMT), N-terminal peptide of MGMT 1999 B Factor 100,000,000 (IPCR 1 molecule, ELISA 10-100 amol) Case et al. [29, 40]... 

Chatterjee C, Patton GC, Cooper L, Paul M, van der Donk WA. Engineering dehydro amino acids and thioethers into peptides using lacticin 481 synthetase. Chem. Biol. 2006 13 1109-1117. 

III this case the two steps, 3-eliminati6n and hydrolysis of the resulting dehydro enzyme were done simultaneously. This procedure may facilitate the task of establishing the chemical structure of the active site of esterases and peptidases (cf. Cohen et al., 1959 cf. TomaSek et al., 1960 Sanger and Shaw 1960). Complications may arise here through base-catalyzed dis-mutations of pyruvoyl peptides, which are observed in the conversion of pyruvoylglycine into alanine by the action of base (Fu et al., 1952 cf. Wieland et al., 1958). 

For example, P. Mathur, S. Ramakumar and V. S. Chauhan. Peptide design using alpha, beta-dehydro amino acids from beta-turns to helical hairpins. Biopolymers, 76 (2004), 150-61. 

Patel, H. C., Singh, T. P., Chauhan, V. S., and Kaur, P. (1990) Synthesis, crystal structure, and molecular conformation of peptide N-Boc-L-Pro-dehydro-Phe-L-Gly-OH. Biopolymers29, 509-515. 

Lantibiotics are small, membrane-active peptides (< 5 kDa) containing the unusual amino acids lanthionine, P-methyl-lanthionine, and the dehydrated residues dehydro alanine and dehydrobutyrine e.g. nisin, lacticin 481, carnocin U-149, lactocin S, sublancin 168 [29-38]. The intrachain positioning of these polycyclic structures of the lantibiotics has been used to group them into linear (Group lA) or circular (Group IB) lantibiotics [39]. Based on similarities in the... 

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