Proline-containing peptides

Regulator activity of the simplest proline-containing peptides PG, GP, PGP, and GPGG, and possible sources of their biosynthesis 98MI10. 

Fig. 8 Separation of D- and L-proline aFGF peptides using neutral and heparan sulfate-coated capillaries. A racemic mixture of D- and L-proline-containing peptides (130 /rM) were injected (22 nL) and subjected to electrophoresis using 50 mM sodium phosphate buffer, pH 7.4, 20C, and 20 kV. (From Ref. 73.)...

Enzymatic Digestion of Proline-Containing Peptides General Procedure ... 

Figure 9 Averaged bond lengths and angles for the pyrrolidine ring in proline-containing peptides...

Proline is an exceptional amino acid residue in that the cis-trans equilibrium only slightly favors the trans form in peptidyl-proline bonds. Small proline-containing peptides in solution contain some 5 to 30% of the cis (syn) isomer, as opposed to less than 0.1% of the cis isomers of the other amino acids.14 The cis form is even found in native proteins two of the four prolines in ribonuclease A... 

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. 

The tripeptide amide L-Pro-L-Leu-Glyamide (melanostatin) is a hypothalamic hormone and an effective therapeutic chelating agent. Its chelating properties have been examined by Kozlowski and his co-workers59 because of thdr interest in proline-containing peptides (Chapter 20.2). With Cu11... 

At the time the work on the alanine tripeptide was published, it was considered nearly an act of heresy to postulate a solution structure for peptides with less than 25 amino acids. This was because techniques for monitoring solution conformation of peptides of this size often were unable to detect a preferred structure, and consequently, the notion developed that small peptides had no solution structure. In this work, we postulated that peptides as small as a tripeptide may exist in a set of preferred structures on the time scale of molecular vibrational transitions. This contention has been further confirmed by us via VCD studies on other alanine peptides, and by the VCD results on small proline-containing peptides [39,47], and more recently by NMR studies [4]. These results will be discussed next. 

Many natural channels, particularly those for simple ions, form at the confluence of complex proteins. This mechanism has been simplified by the Gokel group which has prepared alkyl-terminated hexapeptides that contain a short proline containing peptide sequence, GGGPGGG, similar to that found in natural Cl -selective channels [14], These compounds give Cl- selectivity when anchored in phospholipid vesicles. It is assumed that channels form by supramolecular aggregation of the hexapeptides around the proline motif, shown in Fig. 5.6. Such a simple transport mechanism has yet to be seen in Nature but it would not be too surprising if one were to be found. 

Notice in Table 24-2 how proline is different from the other standard amino acids. Its amino group is fixed in a ring with its a carbon atom. This cyclic structure lends additional strength and rigidity to proline-containing peptides. 

Dipeptidyl peptidase IV hydrolyzes Xaa-Pro-Yaa- peptides to Xaa-Pro and Yaa-, while amino peptidase-P cleaves on the amino side of Pro. These two enzymes are found in the microvillous fraction of rabbit kidney. Catalysis is nonspecific with respect to Xaa and Yaa, except the Yaa position cannot be occupied by Pro or Hyp. Harada et al. have published several papers on assaying cleavage of proline-containing peptides found in structural proteins. 

H. A. Scheraga, ]. Rhys. Chem., 96, 6472 (1992). Energy Parameters in Polypeptides. 10. Improved Geometrical Parameters and Nonbonded Interactions for Use in the ECEPP/3 Algorithm, with Application to Proline-Containing Peptides. 

The formation of the diketopiperazine ring from proline-containing peptides can occur in two ways (see type A and type B). Entropy considerations predict that type A syntheses should result in relatively easier cyclization than type B syntheses. In both approaches, the presence of a proline residue in the peptide allows ready cyclization to the diketopiperazine under conditions which would leave other nonproline-containing dipeptides unaffected. ... 

The ubiquitous nature of proline-containing peptides results in the common appearance of perhydro-l,4-dioxopyrrolo[l,2-a]pyrazines as a result of metabolic processes, particularly of microorganisms. For example, the diketopiperazines 152 were found to be metabolic products of the algae species Scenedesmus sp. These compounds have also been found in cultures of Sfreptomyces. " Glycyl-L-prolyl diketopiperazine has recently been isolated from the small sea animal Luidia clathrata The anhydrides 152 were not directly formed from the constituent amino... 

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