Asn-hexapeptides

GGVIPN (= Gly-Gly-Val-Ile-Pro-Asn) (hexapeptide) Triticum aestimm (wheat) (Poaceae) [wheatgerm proteolytic hydrolysate] ACE (0.7)... 

Oliyai et al. [23] studied an Asn-hexapeptide (Val-Tyr-Pro-Asn-Gly-Ala) in lyophilized formulation as a function of pH of the bulk solution, temperature, and residual moisture content in a factorial study. A statistically significant two-factor interaction indicated that the pH of formulation solution determined the extent to which this peptide stability depends on moisture level and temperature. 

Table 14. The Effect of the Amino Acid Residue on the C-terminal Side of Asn on the Deamidation of Asn-Hexapeptides ...

Figure 210. Arrhenius plots for chemical degradation of two Asn-hexapeptides and salmon calcitonin in aqueous solution. A, Val-Tyr-Pro-Asn-Gly-Ala, pH 7.5 , Val-Tyr-Pro-Asn-Val-Ala, pH 7.5 , salmon calcitonin, pH 6.0. (Reproduced from Refs. 790,791, and 876 with permission.)...

With continuous development of systems for controlled drug release, new materials are being used whose influence on peptide stability must be carefully examined. Thus, the model hexapeptide Val-Tyr-Pro-Asn-Gly-Ala (Fig. 6.30) embedded in poly (vinyl alcohol) and poly(vinyl pyrrolidone) matrices had rates of deamidation that increased with increasing water content or water activity, and, hence, with decreasing glass transition temperature (Tg). However, the degradation behavior in the two polymers differed so that chemical reactivity could not be predicted from water content, water activity, or T% alone. Furthermore, the hexapeptide was less stable in such hydrated polymeric matrices than in aqueous buffer or lyophilized polymer-free powders [132],... 

Thus, the rate of cyclic imide formation of the Asn-Leu hexapeptide at pH 7 was approximately 50 times slower than for the Asn-Gly hexapeptide because of steric hindrance by the leucine (Leu) side-chain. ... 

There have been relatively few reports of the influence of temperature on the rate of deamidation. Deamidation of peptides containing Gin and Asn has been reported to proceed at a higher rate as the temperature was increased. From a study of the deamidation rates of an Asp residue in a model hexapeptide it was... 

Studies of the rates of deamidation in a series of nonaqueous solvents have indicated a dependence of rate on the dielectric constant of the solvent. Although these experiments have generally involved solvents unsuitable for use in formulation, it is interesting to note a reported decrease of the rate of deamidation of N-terminal-blocked Boc-Asn-Gly-Gly in ethanol" (Boc = butoxycarbonyl). Similarly, the deamidation rate of the hexapeptide Val-Thr-Pro-Asn-Gly-Ala decreased with decrease in the dielectric constant of the solvent, an effect which was attributed to the destabilisation of the deprotonated peptide bond nitrogen anion which is involved in the formation of the cyclic imide intermediate. 

The deamidation rate of the hexapeptide, Val-Tyr-Pro-Asn-Gly-Ala (pH 6.8), was also characterized in poly(vinyl alcohol) (PVA) and poly(vinyl pyrrolidone) (PVP) (Lai et al., 1999a Lai et al., 1999b Lai et al., 2000 Song et al., 2001). The rate of deamidation was observed to increase with increasing water content... 

Finally, it was noted that during the deamidation studies in PVP and glycerol, mass balance was not observed (D Souza et al., 2003). Samples containing Val-Tyr-Pro-Asn-Gly-Ala (pH 7.5) with PVP and glycerol were degraded until aplateau was reached at 30% peptide remaining. A PVP-peptide adduct was isolated, in which the pyrrolidone carbonyl of PVP and the N-terminus of the hexapeptide reacted to form a covalent adduct (D Souza et ah, 2003). Reactions between... 

Using the rat liver enzyme they found that the tripeptide Asn.Leu.Thr was a very poor acceptor, while the addition of a further amino-acyl residue at the A- or C-terminus greatly improved its acceptor function. Moreover, when asparagine was free at the A/-terminal the peptides were less effective acceptors than when the A-terminus was substituted by a 2,4-dinitrophenyl residue. It would appear that the essential feature is that there should not be a charged group too close to the asparaginyl group. Provided that this condition is met, further chain extension at the A/-terminal does not further improve acceptor function. Some such effect may also occur near the threonyl residue, for the pentapeptide Tyr. Asn.Leu.Thr.Ser is only one-fifth as efficient as an acceptor as is the hexapeptide Tyr.Asn.Leu.Thr.Ler.Val. 

Physalaamin Pyr-Ala-Asp-Pro-Asn-Lys-Phe-iyr-Gly-Leu-Met-NHj, an amphibian tachykinin from the skin of the South American frog Physalaemus fus-cumaculatus [V. Erspamer et al. Experentia 20 (1964) 489-490]. P. has also been identified as a tumor-related peptide in extracts of human lung small cell carcinoma [L.H.Lazarus etal. Science 219 (1983) 79-81]. It affects blood vessels and extravascular smooth muscle, stimulates exocrine secretion, and has a distinct neurotropic effect. The C-terminal hexapeptide from P. elicits full biological response in guinea pig ileum, while the presence of the five V-terminal amino acids is necessary for full expression of sialogogic activity. Conformational studies have been reported. [J.-L. Bernier et al. Eur. J.Biochem. 142 (1984) 371-377]... 

Melanotropin releasing factor (MRF), melanotropin releasing hormone, melanoliberin a hormone which corresponds structurally to the open hexapeptide ring of Oxytocin (see), without the tripeptide side chain, i. e. Cys-Tyr-Ile-Gln-Asn-Cys. 

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