Sequence isomer, peptide

Problem 20,20. The number of constitutional isomers (i.e., different amino acid sequences) for peptides containing one each of n different amino acids is n (n factorial). What is the number of isomers for peptides containing one each of four different amino acids Of 10 different amino acids ... 

When peptides containing four cysteine residues in the molecule are randomly oxidized, three different disulfide isomers can be formed (Scheme 1), isomer 1 with the disulfides aligned in parallel manner, isomer 2 with crossed disulfides and isomer 3 with sequential disulfides these isomers are also named in a more descriptive manner as the ribbon, globule and string-of-beads isomers. 28 The preferred formation of one of the isomers strongly depends upon the sequential topology of the cysteine residues, but also upon the sequence composition that may favor more or less globular structures with hydrophobic cores. 

When air oxidation of the reduced p-conotoxin GIIIB (18) was carried out in 0.1 M NHtOAc buffer (pH 7.5) at 0.01 mM peptide concentration and at 10 °C, three major products, isomers 15,16, and 17 were produced after 40 hours in a ratio of 1 4 3 (Figure 2). 86 The disulfide structures of each isomer were determined by enzymatic digestion followed by amino acid analyses, mass spectrometry, sequence analyses, as well as by the synthetic approach (Scheme 10). 

The occurrence of the ds-isomer in a tertiary amide bond. 19-21 N-Alkylated amides normally exhibit a mixture of cisltrans-isomers that equilibrate in the order of seconds (AG+ 18-20 kcal-mol-1). The situation is shifted from a pure trans configuration in a secondary (—NHCO—) peptide bond to an equilibrium of both isomers of similar energy upon N-alkylation the percentage of ds-isomer depends upon both the solvent and the sequence. The ds-peptide bond 22-27 is observed between the N-alkylated and the preceding residues in the chain. It is evident that Xaa-Pro peptides will behave similarly. 

Thioesterases of AC V synthetases differ from other thioesterases integrated in nonribosomal peptide synthetases in their direct association with an epimerase domain. A comparison of the primary sequences reveals significant differences to other NRPS thioesterases shown in Table 9. So the GXSXG motif may be involved in the control of tripeptide epimerization by selection of the isomer to be released. Finally, the data support the presence of LLL-AC V as an intermediate in penicillin biosynthesis. 

Mimicking syn-prolines was achieved by different strategies, for example by substitution of the amide for a rigid alkene [13]. Maximizing steric repulsion between the proline ring and the adjacent N-terminal amino acid by attachment of bulky substituents to the heterocycle has also met with some success as exemplified by compounds a [14] and b [15] in Figure 1.2.4. Proline derivatives like a, for example, were incorporated into model peptides and shown to exist predominantly in syn form in water (44—84% syn isomer depending on the peptide sequence) [16]-... 

Fig. 3. Schematic representation (not to scale) of the amino acid sequence of the A-S-B2 isomer of laminin. Laminin is composed of one long arm (A) and two short arms (S and B2) arranged in a cruciform configuration 70 nm long and 70 nm wide. The arginine-glycine-aspartic acid adhesive peptide ( ) starts at peptide sequence 2534 in chain A. (The schematic was redrawn using information obtained from the following references Ayad et al, 1994 Mathews and van Holde, 1990 and Darnell et al, 1990.)...

Interest in making non-native isomers arises because peptide analogues are widely regarded as valuable drug leads and in recent years there has been much effort directed towards the development of peptide libraries. It has been of particular interest to develop methods to increase the surface variability of peptides because the diversity of peptide libraries is, to some extent, limited by the use of the 20 natural amino acids. The study described above shows that the use of alternative disulfide bond connectivities provides another way of altering molecular conformations without modifying the sequence. 

The mass difference between consecutive ions within a series allows the identity of the consecutive amino acids to be determined (see Table 8.2) and thus deduction of the peptide sequence. Indeed, the 20 common amino acid residues have distinctive elemental compositions and consequently distinctive masses. There is one exception with Leu and He, which are isomers. However, a low-accuracy measurement may be incapable of discriminating between Gin and Lys, which differ by 0.036 u. In addition, there are combinations of amino acid residues that yield the same nominal mass or even the same elemental composition. 

In order to be able to predict the retention behavior of peptides of different composition, of peptides of the same composition but different sequence (positional isomers), and of diastereoisomeric peptides, a knowledge of the incremental contribution of each amino acid to the overall contact area term is required not only for each well-defined stationary phase but also for each mobile-phase condition. Group retention coefficient summation approaches based on the assumption that selectivity differences can be ascribed predominantly to amino acid sequence differences, have been developed by Meek (46a, 52b) and Su et al. (45a). These treatments have subsequently been applied to a number of different elution systems (52c-52e). A comparative analysis of the different amino acid group contribution coefficients derived for phosphate, perchlorate, pyridine/acetate, trifluoroacetate, and bicarbonate buffer systems has been reported (52f). 

A detailed investigation of configurational isomers has been carried out with a view to the development of a peptide sequencing process. " Quite good developments towards a practical sequencing process have been made using simple peptide cobalt(III) complexes of triethylene-tetramine and tris(2-aminoethyl)amine (Scheme The critical A-terminal complexes can... 

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