26-Residue peptide

EMPl, selected by phage display from random peptide libraries, demonstrates that a dimer of a 20-residue peptide can mimic the function of a monomeric 166-residue protein. In contrast to the minimized Z domain, this selected peptide shares neither the sequence nor the structure of the natural hormone. Thus, there can be a number of ways to solve a molecular recognition problem, and combinatorial methods such as phage display allow us to sort through a multitude of structural scaffolds to discover novel solutions. 

The Liskamp group also examined the ability of peptoid-peptide hybrids to be bound by the MHC Class II receptor, an important component of the human immune system [39]. Two of three peptoid substitutions in the 14-residue peptide caused substantial decreases in binding affinity, despite the fact that these were solvent-exposed residues. These results were attributed to a loss of hydrogen-bond contacts as well as to steric clashes caused by unfavorable positioning of the new side chain groups. 

Fig. 24. Proposed structure of the Gramicidin A dimer showing the intramolecular and intermolecular hydrogen bonding arrangement. Numbers refer to the amino acid residues Peptide side groups are omitted for clarity.

All eight peptides are of new design and are built of different types of amino acids. Thus, peptides A to E are composed of /3-amino acid residues, peptides F and G of a-amino acid residues, and peptide H of o -aminoxy acid residues. Their structural formulas are shown in Figure 1. 

Human amylin, or islet amyloid polypeptide (hlAPP), is a 37-residue peptide hormone which forms both intracellular and extracellular (EC) amyloid deposits in the pancreas of most type II diabetic subjects. The core of the structure in the SDS micelle is an ot-helix that runs from about residues 5-28. Although the basic structural unit in the fibrils in... 

As in 53 (Scheme 9), the residual peptide sequence C-terminal to pTyr was exchanged against a non-peptide moiety. However, the low affinity of 54 can probably be attributed to an increased flexibility. Comparing 54 with the Grb2-targeted peptidomimetics 41, 42, or 43, it is reasonable to assume that the module C-terminally attached to pTyr in 54 serves as a tripeptide mimetic. 

A. Crystal Structure of a Seven-Residue Peptide from Sup35p. 162... 

Recently, a seven-residue peptide from the Sup35p prion domain has been analyzed by X-ray crystallography (Nelson et al., 2005). Although there is, in general, little reason to suppose that a short peptide will assume the same structure in a crystal as it will in the context of a folded protein containing it, these crystals seem to be related to amyloid fibrils of the same... 

A cross-// spine structure consists of two or more flat or twisted //-sheets, composed of parallel (Nelson et al., 2005) or antiparallel (Makin et al., 2005) //-strands, in a cross-/ arrangement. The cross-/ spine model of fibril formation proposes that a short segment of the native protein changes conformation to form one or more //-strands of a cross-/ spine. The seven-residue peptide GNNQQNY, derived from the prion-determining domain... 

Gorevic, P. D., Castano, E. M., Sarma, R., and Frangione, B. (1987). Ten to fourteen residue peptides of Alzheimer s disease protein are sufficient for amyloid fibril formation and its characteristic x-ray diffraction pattern. Biochem. Biophys. Res. Commun. 147, 854-862. 

In tomato and potato plants, two families of Pis have been identified that show wound-inducible expression. Within 48 h after wounding of leaves of these plants, up to 2% of leaf protein content is made up of protease inhibitors. Potato type I (Potl) inhibitors are not only expressed in wounded leaves but also in tissue of leaves away from the site of attack. ° This finding prompted the search for a hormone or inducing factor that carries the signal for enhanced inhibitor expression through the plant system. Systemin, an 18-residue peptide hormone, has since been reported to induce more than 15 genes of defense nature in tomatoes. ... 

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