Host peptide

T. P. Creamer (unpublished results). A plot of estimated (ASA) against %PPII content is given in Figure 5. At first glance, it would appear that there is little correlation between the two properties. However, three residues—proline, glycine, and glutamine—can be considered outliers, each for a specific reason. Proline has a high %PPII content in the polyproline-based host peptide used by Kelly et al. (2001) as a result of its unique properties as an imine. As discussed above, a proline that is followed in sequence by a second proline is restricted to the PPII conformation by steric interactions. 

Fig. 21. Binding equilibrium between host peptide 64 and guest peptide 65 [51]...

Chimeric peptides are unnatural constructs consisting of bioactive compounds from at least two different peptide(s) and/or protein(s) or two sequences from different parts of the same protein. Such multifunctional peptide combinations are prepared to enhance the biological activity or selectivity of their components. New biological effects can also be achieved with the chimera. In this chapter the synthesis of three different types of chimeric peptides will be described. In a linear chimera, two peptide epitopes from different parts of glycoprotein D (gD) of herpes simplex virus (HSV) are combined. A branched chimera, built from linear peptides, consists of tuftsin oligomers with immunostimulatory activity and an epitope peptide of HSV gD. The third compound is a cyclic chimeric molecule, where a-cono-toxin GI as a host peptide is modified by the incorporation of a core epitope from HSV gD as a guest sequence. 

The three-dimensional geometry of the active site of the enzyme perfectly accommodates to the shape and separation of the amino acids of its substrate. Because the substrate has unnatural stereochemistry at the critical residues, this enzyme is not expected to attack host peptides or even other bacterial peptides composed of natural amino acids. 

Both Pro and Gly have to be considered unusual among the 20 naturally occurring a-amino acids. Their significant influence on the conformation of a host peptide could a priori be expected from a look at the conformational energy maps (Rama-chandran maps) of fiiese two residues. To make it possible to extoid the host-guest principle to amino acids with less dramatic conformational behavior, the original approach was modified such as to insert two vicinal guest residues into the host sequence. 

Two guest amino acids (G) are incorporated into two adjacent positions of a host peptide which is potentially able to exist in a random coil, a-helical and p-sheet conformation, depending on the expo imental conditions. The guest amino adds are supposed to alter the conformational state of the sequence reflecting the strudural preferences of the guest ... 

This is an important prerequisite for its usefulness as a host peptide which should... 

Importance of the position which the guest residue (G) occupies in the host peptide. From these investigations asymmetric conformation nucleation properties of the guest amino acid might possibly be derived. 

Bode et al. incorporated pairs of guest amino acids X and Y into an alaninic host peptide resulting in a sequence of the type Boc-(L-Ala)2-X-Y-(L-Ala)2-NH-POE. The choice of X and Y referred to results from statistical investi tirms on protdns which indicated different probabilities of the selected pairs to occur in the relevant positions i + 1 (X) and i + 2 (Y) of a p-tum... 

Kim, C.A., Berg, J.M. Thermodynamic fl-sheet propensities measured using a zinc-finger host peptide. Nature 362, 267-270 (1993). doi 10.1038/362267a0... 

The cryptophane is typical of the chiral resolution of methane derivatives (eg, CHFClBr) (146) and the basket-shaped host of Figure 23d exhibits extremely high enantioselectivity for various peptides (144). 

One of the early vaccine candidates was directed against sporo2oites, the form of the parasites that is first injected into the host by a mosquito. With recent development of recombinant techniques, several circumsporo2oite proteins or its related peptides were proposed as the vaccine candidates. Clinical trials have been carried out. The vaccines were immunogenic, but did not provide sufficient protective efficacy (90,91). 

The major stmctural feature of the HAz chain (blue in Figure 5.20) is a hairpin loop of two a helices packed together. The second a helix is 50 amino acids long and reaches back 76 A toward the membrane. At the bottom of the stem there is a i sheet of five antiparallel strands. The central i strand is from HAi, and this is flanked on both sides by hairpin loops from HAz. About 20 residues at the amino terminal end of HAz are associated with the activity by which the vims penetrates the host cell membrane to initiate infection. This region, which is quite hydrophobic, is called the fusion peptide. 

Melanocortin peptides are potent anti-inflammatory agents displaying beneficial effects in diseases ranging from cardiovascular to arthritis to obesity to name a few. Within an inflammatory context, they have the ability to switch off early production of cytokines and at later stages they increase levels of anti-inflammatory proteins that lead to the resolution of the host inflammatory response potentially restoring homeostasis to the tissue. They could eventually be viewed as an alternative to glucocorticoids, as their mode of action often resembles that seen... 

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