Proline peptide

In the native protein these less stable ds-proline peptides are stabilized by the tertiary structure but in the unfolded state these constraints are relaxed and there is an equilibrium between ds- and trans-isomers at each peptide bond. When the protein is refolded a substantial fraction of the molecules have one or more proline-peptide bonds in the incorrect form and the greater the number of proline residues the greater the fraction of such molecules. Cis-trans isomerization of proline peptides is intrinsically a slow process and in vitro it is frequently the rate-limiting step in folding for those molecules that have been trapped in a folding intermediate with the wrong isomer. 

Figure 6.9 (a) Peptide units can adopt two different conformations, trans and cis. In the trans-form the C=0 and the N-H groups point in opposite directions whereas in the c/s-form they point in the same direction. For most peptides the trans-form is about 1000 times more stable than the c/s-form. (b) When the second residue in a peptide is proline the trans-form is only about four times more stable than the c/s-form. C/s-proline peptides are found in many proteins. 

F. X. Schmid, R. Grafl, A. Wrba, and J. J. Beintema, Role of proline peptide bond isomerization in unfolding and refolding of ribonuclease, Proc. Natl. Acad Sci. U.S.A. 83, 872-876 (1986). 

Introduction of one azetidine unit in proline peptides reduces the conformational mobility (78MI2). 

A large number of 13C NMR studies on proline derivatives and proline peptides have appeared in the literature [815-830]. As the electron charge density of cis-proline carbons is different from that of franx-prolinc carbons, these isomers can be differentiated by nCNMR spectroscopy [826, 830]. On the basis of calculations Tonelli [831] predicted four conformations for the dipeptide Boc-Pro-Pro-OBzl, three of which could be detected by 13C NMR spectroscopy [826, 830], In proline-containing peptides the stereochemistry of the proline residue plays an important role for the conformation of these oligomers. The 13C chemical shift data of cis and trans proline derivatives, collected in Table 5.29, are useful to determine the stereochemistry of the amino acid-proline bond, e.g. in cyclo-(Pro-Gly)3, melanocyte-stimulating hormone release-inhibiting factor or thyrotropin-releasing hormone. 

In the synthesis of l,2,5-triazepine-l,5-diones, which are expected to mimic the structural features of or-peptidyl prolin-amides, the preparation of N2,N3-disubstituted derivatives 213a from the reaction of (Z)-alanine with the N2-substituted triazepines 213 resulted in lower yields. It has been reported that these fused triazepinediones could be elaborated to give constrained rir-peptidyl proline peptide mimetics of defined stereochemistry and sequence <1997J(P1)2297>. 

Schanze and Sauer were the first to report a detailed study of long-range photoinduced ET in a series of metal-organic dyads [94]. These authors synthesized dyads 50a-e (Scheme 22 and Table 4) that comprise a Ru(diimine) + chromophore covalently linked to a p-benzoquinone acceptor using a series of oligo-L-proline peptide spacers. Oligo-proline peptide spacers are used because previous studies suggest that these peptides are conformationally restricted and... 

Bause E. Structural requirements of iV-glycosylation of proteins. 43. Studies with proline peptides as conformational probes. Biochem. 

The Af-acyl groups in bound proline and hydroxyproline differ from all the other peptide groups in being fully substituted tertiary amides. Whereas secondary peptides (XXXIX) may form anions (XXXX) by abstraction of a proton from the nitrogen atom, the formation of an anion (XXXXII) from a proline peptide (XXXXI) would have to proceed with cleavage of... 

The strong influence of proline on the conformation of the preceding residue reflects steric clashes involving the pyrrolidine ring. Of proline peptide bonds in secondary structures, 38% are found in loops or random coils, 26% appear in helices, 23% in turns, and 13% in /1-strands [93],... 

Theoretical calculations showed that in a-helices trans proline peptide bonds can best be accepted up to the fourth position within the helix because there is neither a disruption of the hydrogen bonding network in this region nor does the bulk of the pyrrolidine ring seriously interfere with the regular helix geometry. Analyses of the Brookhaven database in 1991 also showed that the highest fre-... 

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