Y-Peptide

FIGURE 5.10 Effects of co-expressed G-protein (G ) on neuropeptide NPY4 receptor responses (NPY-4). (a) Dose-response curves for NPY-4. Ordinates Xenopus laevis melanophore responses (increases light transmission). Ordinates logarithms of molar concentrations of neuropeptide Y peptide agonist PYY. Curves obtained after no co-transfection (labeled 0 jig) and co-transfection with cDNA for Gai6. Numbers next to the curves indicate jig of cDNA of Ga]g used for co-transfection, (b) Maximal response to neuropeptide Y (filled circles) and constitutive activity (open circles) as a function of pg cDNA of co-transfected G g. 

Michel MC, Beck-Sickinger AG, H Cox et al (1998) XVI. International Union of Pharmacology recommendations for the nomenclature of neuropeptide Y, peptide YY and pancreatic polypeptide receptors. Pharmacol Rev 50 143-150... 

Fig. 2.16 Effect of electrostatic interactions on 3i4-helix formation in an aqueous environment [1 75 a, 175 b, 176]. y -Peptides 86 and 87 adopt a stable helical conformation mediated by salt bridges near neutral pH. While the propensity of these peptides to adopt a helical conformation is strongly de-...

Fig. 2.21 Water soluble y -peptides incorporating y -amino acid residues constrained with five-membered rings that fold into the 2.5i2-helical secondary structure [121, 123-125]...

Homologs of yS-peptides with one additional methylene group inserted into the backbone of each residue, namely y-peptides (Fig. 2.33), also form well-defined... 

Substitution patterns in y peptides that lead to defined secondary structures R R2... 

Fig. 2.33 Classification of y-peptides according to their substitution patterns (Seebach s nomenclature) and folding propensity...

This effect is particularly well documented for y - and -amino acid residues [217, 218] which in several natural products (bleomycin A2 [219], calyculins [220]) have been shown to play a substantial role in the pre-organization of the whole molecule into its bioactive conformation. For example, changes in the substitution pattern of the y-amino acid linker in bleomycin A2 result in reduced DNA cleavage efficiency [219]. In the case of y-peptides, changing the relative configuration like or unlike of y " -amino acids has been used as a strategy to generate different local conformations (Fig. 2.34) suitable either for the construction of helices [201] or turns ]202-204]. 

Alternatively, rigidification of the y-peptide backbone to avoid H-bonds between nearest neighbors can be achieved by the introduction of an a,y9-unsaturation into the backbone of each y-amino acid constituent (vinylogous peptides) ]208, 209]. Recent ab-initio calculations suggested that the a,/9-unsaturated y-peptide backbone might support the formation of helices with large 19- and 22-membered H-bonded pseudocycles ]221]. 

Preparation of y-Amino Acid Monomers for y-Peptide Synthesis... 

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