Threonine-containing peptides

FIGURE 8.8 A peptide sequence containing an oxazolidine ring that gives rise to a serine residue on acidolysis and a thiazolidine ring that gives rise to a cysteine residue on acidolysis. Substituents at C-2 can be H2, H,Me, or Me2. A structure with a methyl group at C produces a threonine residue on acidolysis. 

Another possible method for the selective introduction of thioamide bonds into cyclic peptides is the use of oxazoles. 513-515 The oxazoles, which can be generated in serine- or threonine-containing peptides by the use of the Burgess reagent [(methoxycarbonyl-sulfamoyl)triethylammonium hydroxide inner salt) or under Mitsunobu conditions (see Section 6.8.5.2.2.2), are thionylated with hydrogen sulfide and triethylamine. A disadvantage of this method is that it is limited to serine- and/or threonine-containing peptides. 

Examples of the cyclodehydration of peptide segments containing serine or threonine residues or the corresponding oxo amides to oxazoles are given in Table 2, Section 11.2.3.5. 

Recently, samarium diiodide was discovered to initiate the same fragmentation process with the threonine-containing peptide 34 (Scheme 19b) as well as to promote C - C bond formation after reduction of the glycyl radical intermediate, as discussed in Sect. 2.1.2 [26]. The method suggests the possibility of functionalizing peptides very simply and in only two steps. 

M - HJ- Ion of Threonine. The [M - H] ion of threonine undergoes several reactions under MS/MS conditions. Perhaps the most structurally diagnostic reaction of threonine and threonine-containing peptides is the loss of acetaldehyde. A mechanism involving an elimination induced by intramolecular pro-ton transfer has been proposed [Eq. (10)] [38]. 

The cyclamides are small cyclic peptides that characteristically contain multiple thiazole, thiazoline, oxazole, and oxazoline rings, which are derived from cysteine, serine, and threonine residues. Some of the first examples of this class to be described were the patellamides (53-55) from the tunicate Lissoclinum patella, although it was later determined they were produced by the symbiotic cyanobacterium Prochloron sp. The structures were solved by a combination of acid hydrolysis and GC analysis, coupled with 2D NMR. Smaller cyclic peptides from this class include the hexapeptides westiellamide (56) and microcyclamide (57) from M. aeruginosa Many members of the class possess cytotoxic properties, although their biological function or mechanism of action is not fully understood. In contrast to many cyanobacterial peptides, aside from the unusual heterocyclic residues, these peptides generally contain only ribosomal amino acids. 

C. Synthesis of O-Sulfonated Serine- and Threonine-Containing Peptides... 

At the end of this chapter, cyclic peptides will be mentioned one of them (a mixture) being indeed the first antibiotic peptide ever isolated actinomycin from cultures of Streptomyces antibioticus by Waksman and Woodruff in 1940. The different actinomycins are orange-red peptides all containing the same chromo-phore, an aminophenoxazinone dicarboxylic acid, whose carboxyl groups are connected via the amino group of threonine with two identical cyclic depsipep-tide rings consisting of five amino acids. In Fig. 28 the cyclic part of actinomycin C3 is depicted as determined by H. Brockmann (Plate 13) and associates, who in the fifties contributed most to the analytical and synthetic chemistry of this class of compounds. 

Post-source Decay Tandem Mass Spectrometry The potential of PSD has also been exploited to identify phosphopeptides [61,62]. This technique is used for MALDI-generated ions in a reflectron TOP instrument. PSD can also distinguish any serine-threonine phosphorylation from tyrosine phosphorylation. Phosphotyrosine-containing peptides mostly yield the [MH — HP03J+ (loss of 80 Da) ion, whereas phosphoserine- and threonine-containing peptides produce [MH - H3P041+ (loss of 98 Da) and [M - HP03]+ ions. 

Rearrangement reactions occur with serine- and threonine-containing peptides. 

Borner and coworkers used acid phosphatase to induce microstructure formation. The peptide-segment contained three phosphothreonine residues in the (TV)s peptide motif of the peptide-PEO conjugate, which prevented p-sheet formation. Enzymatic dephosphorylation of the threonine side chains therefore induced self-assembly of the bioconjugate. 

Maeji, N. J., Inoue, Y., and Chujo, R., 1987, Preliminary communication The role of the N-acetyl group in determining the conformation of 2-acetamido-2-deoxy-D-galactopyranosyl-threonine-containing peptides, Carbohydr. Res. 162 4-8. 

The formation and dissociation of phosphotylated peptide radical cations [pM] has been studied. Phosphoserine- and phospho-threonine-containing peptide radical cations were formed by low-energy collision-induced dissociation (CID) of the ternaiy metal-ligand... 

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). 

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