Tryptophan containing peptides

The highly regioselective hydrolysis of tryptophan-containing peptides with the [Pd(en)]2+ (en = H2NC2H4NH2) complex has been reported by Kostic and co-workers.436 The hydrolysis does not proceed without the palladium(II) complex. However, when equimolar amounts of a... 

Fig. 10. Highly schematic representation of the orientation of several tryptophan-containing peptides with respect to calmodulin. (A) With tryptophan in position 1, the indole is located on the hydrophilic side of the helix and is exposed to solvent. Peptides with tryptophan on this face of the helix should exhibit emission maxima near that of indole in water ( 350 nm), a small anisotropy, and a high accessibility for acrylamide quenching. (B) In position 2, the tryptophan is partially exposed at the interface between the peptide and calmodulin. Peptides with a tryptophan in this location should have fluorescence properties that are intermediate between example A and C. (C) The tryptophan is on the hydrophobic side of the helix and is almost entirely buried. The emission maximum should be strongly blue-shifted, the anisotropy should be large, and the accessibility to acrylamide quenching low. Taken from O Neil et al. (1987).

Fig. 11. Variation of the fluorescence properties of a set of tryptophan-containing peptides as a function of the position of the tryptophan in their sequence. The parameter/AVe describes the degree of rigidity and hydrophobicity of the tryptophan s environment it is based on emission maximum, anisotropy, and accessibility to acrylamide. When the values for each of these parameters were similar to those expected for indole in water, a value near 0 was assigned to/, whereas values up to 1.0 were assigned as the fluorescence parameters more closely resembled those observed in very rigid and apolar environments such as the interior of a protein or ethylene glycol at -60°C (Lakowicz, 1983). The values of / calculated for each parameter were then averaged to give /AVe- The dotted curve was generated by fitting a sine wave to the data (period = 3.3 residues). Taken from O Neil et al. (1987).

Eoettinger A, Leitner A, Lindner W. Selective enrichment of tryptophan-containing peptides from protein digests employing... 

Li XF, Zhang LS, Hall SE, Tam JP. A new ligation method for N-terminal tryptophan-containing peptides using the Pictet-Spengler reaction. Tetrahedron Lett. 2000 41 4069-4073. 

In a few cases, alkaline hydrolysis has proved applicable to special problems. Tryptophan is not destroyed in alkali, and analysis of alkaline hydrolyzates forms the basis of one method for quantitative determination of this amino acid (e.g., Dreze, 1960). Despite the fact that tryptophan-containing peptides should be more stable in alkali than acid, partial alkaline hydrolysis has not been employed for identification of this type of peptide. Amino acids often can be regenerated by alkaline hydrolysis from derivatives obtained by the amino-terminal end-group methods. Dinitrophenyl amino acids and phenylthiohydantoin (Fraenkel-Conrat et al., 1955) as well as hydantoin (Stark and Smyth, 1963) derivatives of amino acids can be treated in this manner. 

Toulme, J. J., Charlier, M., and Helene, C., Specific recognition of single-stranded regions in ultraviolet-irradiated and heat-denatured DNA by tryptophan-containing peptides, Proc. Natl. Acad. Sci. U.S.A., 71(8], 3185, 1974. 

Dimicoli, J. L. and Helene, C., Interactions of aromatic residues of proteins with nucleic acids. I. Proton magnetic resonance studies of the binding of tryptophan-containing peptides to poly(adenylic acid) and deoxyribonucleic acid, Biochemistry, 13(4], 714, 1974. 

A few instances of pyrrole-, indole-, carbazole-containing natural products are known from insects and higher animals, in addition to tryptophan-containing peptides. 

Oxidation of indoles. Tryptophan and related 3-substiluted indoles are oxidized to oxindoles in high yield by DMSO and cone. HCl (equation 1). This reaction can be used for modification of tryptophan-containing peptides and proteins. ... 

Calmodulin does not contain any tryptophan residues, allowing observation of tryptophan-containing peptides in the presence of calmodulin. Seventeen MLCK-like peptides were synthesized in wtuch a single tryptophan residue was moved along the sequence."" If these peptides were bound to calmodulin in the a-helical state, then one expects the single tryptophan residue to be buried between the peptide and calmodulin in some trf the peptides, and to be exposed to water in oUict peptides (Figure 16.38). This dependence is expected to repeat with the peiiodici of an a-helix. 

The in-formyl group is cleaved by weak bases such as aqueous piperidine or hydrazine. Its sensitivity to amines can pose some problem in mildly basic media it migrates to a-amino groups. On the other hand, the in-formyl group is indeed able to reduce the extent of alkylation, for instance tert.butylation that occurs during the removal of tert.butyl groups by acidolysis. Also, in N "-for-myl derivatives of tryptophan containing peptides less oxidation takes place in acidic media, a reaction that results in the formation of colored products. 

During operations performed in acidic media tryptophan containing peptides produce yellow, pink or purple colors due to several transformation products... 

In our 1-hydroxyindole hypothesis, we had predicted that 5-hydroxy-tryptamines (serotonins) and 5-hydroxytryptophans were supplied from the 1-hydroxytryptophan residues in the tryptophans-containing peptides by the mediation of acids that are hnked with the TCA (Kreb s) cycle [2,5-7]. 

Several tryptophan-containing peptides have been synthesized recently by SPPS " . Mercaptoethanol and 1,2-dimercaptoethane both appear to be satisfactory for protection of tryptophan in acidic reagents. Hydrolysis of peptides by p-toluenesulfonic acid in the presence of indole 9 allows direct analysis of tryptophan. 

Significant mutagenic activity was detected with pyrolysates of most of the materials tested. The highest mutagenic activity was observed with pyrolysate of a tryptophan-containing peptide. The pyrolysates required a liver microsomal portion, representative of mammalian metabolism, for the detection of mutagens. 

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