Val-Tyr-Pro-Asp-Gly-Ala

Fig. 6.28. Breakdown reactions of Val-Tyr-Xaa3-Asp-Xaa5-Ala as a function of pH (Asu = aspartic succinimide) [93] [96], a) Breakdown reactions of Val-Tyr-Pro-Asp-Gly-Ala in pH ranges 1-3, 4-5, and 6-10. b) Breakdown reactions of Val-Tyr-Pro-Asp-Ser-Ala, Val-Tyr-Pro-Asp-Val-Ala, and Val-Tyr-Gly-Asp-Gly-Ala at pH 1. c) Breakdown reactions of the same...

Further insights into the influence of pH on the reactivity at aspartic acid residues are provided by a study of the model peptide Val-Tyr-Pro-Asp-Gly-Ala (Fig. 6.28,a) [93], At pH 1 and 37°, the tm value for degradation was ca. 450 h, with cleavage of the Asp-Gly bond predominating approximately fourfold over formation of the succinimidyl hexapeptide. At pH 4 and 37°, the tm value was ca. 260 h due to the rapid formation of the succinimidyl hexapeptide, which was slowly replaced by the iso-aspartyl hexapeptide. Cleavage of the Asp-Gly bond was a minor route. At pH 10 and 37°, the tm value was ca. 1700 h, and the iso-aspartyl hexapeptide was the only breakdown product seen. In Sect. 6.3.3.2, we will compare this peptide with three analogues to evaluate the influence of flanking residues. 

Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-Gly-Lys-Lys-Arg-Arg-Pro-Val-Lys-Val-Tyr-Pro-Asn-Gly-Ala-Glu-Asp-Glu-Ser-Ala-Glu-Ala-Phe-Pro-Leu-Glu-Phe (human ACTH) 4Z-Unit Peptides Monotetracontapeptide 81-121 of human growth hormone... 

At pH 10 and 70°, the hexapeptides had tm values for degradation of ca. 30-40 h, with the exception of Val-Tyr-Pro-Asp-Val-Ala, the stability of which was much greater (t1/2 ca. 800 h). Here, the hexapeptides containing Asp-Gly or Asp-Ser were clearly much more reactive than the Asp-Val hexapeptide. Interestingly, the D,L-iso-aspartic hexapeptide was the only product formed from the Asp-Gly hexapeptides, and it was the major product from the Asp-Ser hexapeptide (Fig. 6.28,a and c). Formation of the D-Asp hexapeptide was observed for the Asp-Ser hexapeptide, and it was the major one for the Asp-Val hexapeptide, presumably because base-catalyzed epimerization had ample time to occur given the very slow rate of other breakdown reaction. 

Secreted by the pituitary gland, corticotropin is a hormone that stimulates the adrenal cortex. Determine its primary structure fiom the following information, (i) Hydrolysis by chymotrypsin produces six peptides Arg-Trp, Ser-Tyr, Pro-Leu-Glu-Phe, Ser-Met-Glu-His-Phe, Pro-Asp-Ala-Gly-Glu-Asp-Gln-Ser-Ala-Glu-Ala-Phe, and Gly-Lys-Pro-Val-Gly-Lys-Lys-Arg-Arg-Pro-Val-Lys-Val-Tyr. (ii) Hydrolysis by trypsin produces free lysine, free arginine, and the following five peptides Trp-Gly-Lys, Pro-Val-Lys, Pro-Val-Gly-Lys, Ser-Tyr-Ser-Met-Glu-His-Phe-Arg, and Val-Tyr-Pro-Asp-Ala-Gly-Glu-Asp-Gln-Ser-Ala-Glu-Ala-Phe-Pro-Leu-Glu-Phe. 

Glutathione reductase from yeast and from E. coli contains 4 and 6 thiol groups per FAD, respectively (Table I), in addition to the active center disulfide. Peptides containing 3 of the 4 thiols have been isolated and sequenced Cys-AsnAsp Lys-Ile-Ala-Cys-Pro-Gly-Asn-Val-Gln-Lys Asp-Thr-Ile-Tyr- (His,Glx) -Val-Cys-Lys- (Thr,Gly,Ala,Leu2) (35). The thiols in the yeast enzyme, like those in lipoamide dehydrogenase, are relatively unreactive. Reactivity with phenyl mercuric acetate... 

---