Peptides constitutional isomers

Seebach, D., Abele, S., Gademann, K., Guichard, G., Hintermann, T., Jaun, B., Matthews, J. L., and Schreiber, J. V. (1998). /32- and /3 -peptides with proteinaceous side chains Synthesis and solution structures of constitutional isomers, a novel helical secondary structure and the influence of solvation and hydrophobic interactions on folding. Helv. Chim. Acta 81, 932-982. 

V. Schreiber, L. Oberer, U. Hommel, H. Widmer, P - and p -Peptides with Proteinaceous Side-Chains - Synthesis and Solution Structures of Constitutional Isomers, a Novel Helical Secondary Structure and the Role of Hydrophobic Interactions on Folding , Helv. Chim. Acta 1998, 81, 932 -982,... 

Peptide formation can yield different constitutional isomers, e.g., the reaction of Gly with Ala can proceed in two ways depending on which amine group reacts with which carboxyl group ... 

The order of placement of amino acid residues in a peptide proceeding left to right is referred to as the amino acid sequence or simply sequence. Different amino acid sequences equal different constitutional isomers. 

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 ... 

Problem 20.62. What is the total number of constitutional isomers for the peptide of Problem 20.61 Ans. 51 = 5x4x3x2x1 = 120... 

Ans. This would produce CMP-UMP, a constitutional isomer of UMP-CMP. CMP-UMP and UMP-CMP differ in the sequence of nucleotides, and even more specifically in the sequence of heterocyclic bases. The situation is analogous to the sequence of amino acid residues in a peptide. 

Tantomerization (Section 18.2) An isomerization by which tautomers are rapidly interconverted, as in keto-enol tantomerization. Tautomers (Section 18.2) Constitutional isomers that are easily interconverted. Keto and enol tautomers, for example, are rapidly interconverted in the presence of acids and bases. Terminal residue analysis (Section 24.5) Methods used to determine the sequence of amino acids in a peptide by reactions involving the N- and C-terminal residues. 

The prediction of the partition properties of peptide molecules is difficult, owing to their conformational flexibility, and the possible presence of multiple intramolecular hydrogen bonds and ionizable groups. Richards and coworkers (40-42) were the first to consider explicitly the effects of the population of accessible conformational minima in both phases. These types of calculation are, however, computationally intensive. The introduction of the solvent-accessible surface area in the prediction of log Poct for steric isomers (43,44) also constitutes a promising approach. 

Native FKBP12 contains seven trans prolyl peptide bonds, and the CTIs of some or all of them constitute a slow, rate-limiting event in folding. Its refolding process from a chemically denatured state constituted the first example of an autocatalytic formation of a native protein from kinetically trapped intermediates with nonnative prolyl isomers [76,77]. 

Whereas peptidyl prolyl cis-trans isomerases constitute a well-characterized enzyme class comprising well over 1000 members with small sequence variations in the proteins of different species, the discovery of secondary amide peptide bond cis-trans isomerases (APIases) had to await the development of suitable enzyme assays. Fortunately, spectral differences in the UV region between cis and trans isomers of dipeptides could be exploited to identify and quantify isomerization rate-enhancing factors in biological material [149]. 

The presence of an additional carbon atom between the amino and the carboxy function increases the number of possible constitutional and configurational isomers. Several methods have been developed to prepare N-protected (3-amino acid building blocks for the synthesis of (3-peptide oligomers [95, 96], The Arndt-Eistert homologation and the Evans methodology are two versatile strategies to obtain enantiomerically pure N-protected monomers with the side chains at the C(3) and C(2) carbon atoms, respectively [97, 98],... 

Trans cis isomerization occurs most readily at the Trp-Pro bond, so that populations of corresponding major isomers of zwitterionic forms of the peptides are comparable and constitute a 0.85-0.90 molar fraction of the total peptide content. Isomerization about Pro-Pro bonds in peptides with n > 1 results in a small population of at least two additional cis isomers. The rate constant for interchange between trans and ds isomers about the Trp-Pro bond at 298 K has been estimated to be close to 10 s (3, 35, 38), that is,... 

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