Peptides turns

Fig. 2.29 Comparison of antiparallel hairpins 118 and 119 with non-peptide turn segments.

As a result of their capacity to tolerate very different kinds of y9-peptidic turns (120 versus 122) and different stereochemistries in the turn segment (compare S/ R and R/S nipecotic acid dipeptide sequences), hairpin stmctures formed by fS-peptides reveal unusually high plasticity compared to a-peptide y9-hairpins. 

Further Six-Membered and Seven-Membered Ring Heterocycle Mimics of Peptide-Turn Motifs... 

Kemp and McNamara166 designed and synthesized lactam 13 (Scheme 7) to stabilize the backbone conformation of a rare P-tum involving a di-peptide bond found between the (/ +1)- and (/+2)-residues in a few cyclic peptide turns via C (/) C (/+1) cyclization. 67 However, its incorporation into a bioactive peptide has never been reported. 

Protein-protein interactions usually occur on the surface of proteins where mainly loops or turns are present [24], It is, therefore, of interest to stabilize specific peptide turns and test them for their biological activity [25-28], As discussed, metal coordination seems to be a powerful tool for obtaining macrocycles with a bent peptidic domain simply by mixing metal ions and peptide-bridged ligands. 

Clipping of the linear derivative 4-H4 to fix the WAG-sequence in a bent conformation proceeds smoothly by addition of 02Mo(acac)2 and K2CO3 in methanol. The ds-dioxomolybdenum(VI) complex K2[4MoC>2] is characterized by spectroscopic methods like NMR or ESI-MS. The results obtained indicate that only one of the two possible stereoisomers is formed. This shows that the amino acids of the WAG sequence are able to induce chirality perfectly at the metal complex unit. The good resolution and signal dispersion in the H NMR spectrum indicate the peptide turn adopts a well defined conformation. From the present results, however, it cannot be deduced if this conformation is the biologically active one [34],... 

Some other recent work indicates an apparent qualitative effect on protein synthesis. Ho (31) and Jacobsen et al. (32) detected new peptides when aleurone layers were treated with ABA. These peptides turned over rapidly, and the quantities formed were reduced by inhibitors of transcription and translation. Little else is known currently about the peptides. 

Peptidic p-tum mimetics are generally based on cyclic backbone mimetics (e.g. replacing the turn hydrogen bond by a covalent bond) or by introducing one or several unusual amino acids, which constrain the backbone in P-tum conformations. Synthetic approaches to non-peptidic turn mimetics can be grouped into two classes 1) external P-turn mimetics, and 2) internal P-turn mimetics. ... 

Metallocenes, in particular ferrocene, may also serve as peptide mimetics. Herrick and co-workers were the first to recognize that l,l -disubstituted ferrocene may serve as a peptide turn mimetic, since it holds the two peptide strands in a geometry similar to turn structures found in proteins. Further work by several groups unraveled the rules... 

While predictions are generally not to be trusted, it would still be surprising if the atrial peptides turned to be not just the first but also the last compounds with... 

Partial Hydrolysis and Sequence Comparison In some cases it is also possible to determine the sequence of an unknown polypeptide by sequencing just a few of its amino acids and comparing this partial sequence with the database of known sequences for complete polypeptides or proteins. This procedure works if the unknown peptide turns out to be one that has been studied previously. (Studies of the expression of known proteins is one dimension of the field of proteomics. Section 24.14.) Due to the many sequence permutations that are theoretically possible and the uniqueness of a given proteins structure, a sequence of just 10—25 peptide residues is usually sufficient to generate data that match only one or a small number of known polypeptides. The partial sequence can be determined by the Edman method or by mass spectrometry. For example, the enzyme lysozyme with 129 amino acid residues (see Section 24.10) can be identified based on the sequence of just its first 15 amino acid residues. Structure determination based on comparison of sequences with computerized databases is part of the burgeoning field of bioinformatics. 

To some extent, the structures discussed above resemble turn structures in peptides. A typical peptide turn structure is depicted in Scheme 5.5. Ring constraints by hydrogen bonds define y-turns (7-membered ring) or p-tums (10-membered ring), whereas 13-membered rings are present in a-helices. Before and after the turn, the peptide extends as anti-parallel strands, often in p-sheets... 

Scheme 5.5 Naturally occurring peptide turn structures which are stabilized by hydrogen bonds in comparison to intramolecular hydrogen bonds in 10 and 11.

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