A-helical peptides

Fig. 5.2 The a-helical peptide nucleic acid (aPNA) design concept. (Reprinted with permission from Garner P., Dey S., Huang Y.J. Am. Chem. Soc. 2000, 722, 2405 [51])...

Since our original aPNA publication, there have been other reports of the incorporation of nucleobases into a-helical peptides. Mihara and coworkers reported that a-hehcal coiled-coiled peptides could be stabilized by base pairs between complementary y-nucleobase-a-aminobutanoic acids [78] They have also reported that the incorporation of such nucleoamino acids into a-hehcal segments of HIV-1 Rev and HIV-1 nucleocapsid protein can result in increased binding affinity and specificity to HIV-1 RRE RNA and SL3 RNA respectively [79, 80]. 

A helical peptide backbone. The side chains are omitted to emphasize the shape of the helix. Notice the... 

The use of disulfide linked di-a-helical peptides for the self-assembly of a heme-peptide model compounds has also been explored by Benson et al. (109). Conceptually analogous to the larger heme-protein systems utilized by Dutton and co-workers, to be detailed later, the incorporation of C4 S5mimetric Co(III)-porphyrins, based on coproporphyrin and octaethylporphyrin, resulted in helical induction comparable to that observed in the covalent PSM systems. 

Bl. Baker, H. N., Jackson, R. L., and Gotto, A. M., Cyanogen bromide fragments of the human plasma high density, apoLP-Gln-I Isolation of a helical peptide. Circulation 24, Suppl. II, 255 (1972). Abstr. 

The engineering of zinc-binding sites in a-helical peptides, where metal binding stabilizes protein tertiary structure, has been reported by Handel and DeGrado (1990). In these experiments zinc-binding sites are incorporated into a dimeric helix-loop—helix peptide (H3 2) and a protein composed of four helices connected by three short loop sequences (H3 4). a model of one subunit of the H3 2 dimer is found in Fig. 47. In addition to metal complexation by two histidine residues at positions n and n+4 of one a helix, the metal is coordinated by a third histidine residue of an adjacent a helix. The composition of the zinc coordination polyhedron is like that of carbonic anhydrase (i.e., Hiss), and spectroscopic results suggest that all three histidine residues are involved in zinc complexation. This work sets an important foundation... 

Fig. 47. Model of the a-helical peptide HSaj. showing backbone atoms and three histidine zinc ligands. The bound zinc ion is represented by a sphere. [Reprinted with permission from Handel, T., DeGrado, W. F. (1990) J. Am. Chem. Soc. 112,6710—6711. Copyright 1990 American Chemical Society.]...

Two independent screens have been developed to investigate the effects of fluorinated building blocks on the interactions of the dimeric peptide assembly. The impact of fluorine side chain substitutions on the stability of coiled coil folding has been studied using temperature-dependant CD spectroscopy. The second screen is based on the ability of a-helical peptides to self-replicate. Thus, peptide... 

Model peptides that can adopt the (3-sheet conformation have until recently been confined to ones that form intermolecular (3-sheets, t96,104,105 Peptides that can form intramolecular (3-sheets have been avidly sought because the coil-(3 transition1 06 in such peptides would provide thermodynamic data on the effects of sequence and individual residues on (3-sheet stability like those obtainable from model a-helical peptides. Two types of models have been developed 107 (3-hairpins, i.e. two-stranded (3-sheets, and three-stranded (3-sheets. 

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