| Small independently folding peptide models of {dollar}beta{dollar}-hairpin-like and {dollar}alpha{dollar}-helix-turn-{dollar}beta{dollar}-strand tertiary structures were designed as structural mimetics of loop and helical segments in larger proteins. The {dollar}beta{dollar}-hairpin-like loop model peptide, BB-PND, contains twelve amino acids and has a sequence similar to that of a segment (G-P-G-R) in the V3 loop of the HIV surface glycoprotein, gp120. This segment of the V3 loop contains the principal neutralizing determinant of HIV-1 viruses and is being widely investigated for its role in HIV infection. The seventeen amino acid {dollar}alphabeta{dollar} model peptide, AB-E4, contains a twelve amino acid sequence (E-D-V-R-G-R-L-V-Q-Y-R-G) that is identical to a segment of apolipoprotein E4, with the addition of a short, extended tail segment. This segment distinguishes apo E4 from other apo E isoforms. Apo E4 has also been genetically linked to some forms of heart disease and Alzheimer's disease.; The structures of these peptides and analogues of them were characterized in aqueous solution by circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopies. The number of observed medium to long range rOes was extraordinary for such small peptides in water at 27{dollar}spcirc{dollar}. These rOes also indicate that stabilizing hydrophobic interactions are occurring between adjacent segments and that the peptides adopt the desired tertiary structures. The structural properties of these peptides may be useful in developing general principles for designing structural mimetics of larger proteins that do not require rigid, non-peptide moieties, unnatural amino acids, covalent cross links, or metal binding sites for stability. |
