Mimicry peptidal

The well-defined helical structure associated with appropriately substituted peptoid oligomers (Section 1.6) can be employed to fashion compounds that closely mimic the stracture and function of certain bioactive peptides. There are many examples of small helical peptides (<100 residues) whose mimicry by non-natural ohgomers could potentially yield valuable therapeutic and bioactive compounds. This section describes peptoids that have been rationaUy designed as mimics of antibacterial peptides, lung surfactant proteins, and coUagen proteins. Mimics of HIV-Tat protein, although relevant to this discussion, were described previously in this chapter (Sections 1.3.2 and 1.4.1). 

Patch, J.A. and Barron, A.E. Mimicry of bioactive peptides by non-natural, sequence-specific peptidomimetic oligomers. Curr. Opin. Chem. Biol. 2002, 6, 872-877. 

Their reduced mobility allows them to be used in the study and mimicry of protein folding and serve as valuable models for gaining conformational insight into the properties of larger peptides and proteins. ... 

Structural and Functional Studies of Peptide-Carbohydrate Mimicry... 

Peptide-Carbohydrate Mimicry in Enzyme Active Sites. 93... 

Keywords Molecular modeling NMR spectroscopy Peptide-carbohydrate mimicry Protein-ligand interactions X-ray crystallography... 

In contrast, the existence of peptide-carbohydrate mimicry is more surprising in that it is difficult to picture how these two different classes of compounds could mimic each other. The origin of this effect at the molecular level has been the subject of recent investigations by NMR spectroscopy, X-ray crystallography, and molecular modeling. In combination with functional data, these studies provide insight into the nature of this phenomenon. 

While functional (immunological) mimicry has been established, the basis of mimicry on the molecular level remains to be explained. Several hypotheses have been put forward one of the earliest was that the side chains of aromatic amino acid residues might mimic the hydrophobic faces of the pyranosyl rings of carbohydrates. Before 1997, no structural evidence was available to support or discount these hypotheses. The nature of peptide-carbohydrate mimicry on the molecular level became the subject of structural investigations, and the resulting studies along with functional data will be discussed below. 

Fig. 4 Stereo views (in transparent, space-filling models) of selected hydrophobic interactions in the Fab-peptide and -pentasaccharide complexes. A Trp P3 buried in the hydrophobic cavity formed by CDR L3, His H58 and Trp H47. B Interactions of the side chain of Met P5 with Trp H33. C and D Interactions of the peptide and pentasaccharide, respectively, with His L27D and Tyr L32 (the pocket which accommodates the GlcNAc D methyl group). In (C) the hydrogen bond between the Asp P2 side chain and His L27D NE2 is also shown. A corresponding hydrogen bond between Rha Al 3-OH and His L27D NE2, shown in (D), represents an element of structural mimicry. Reproduced from [80]. 2003 by The National Academy of Sciences of the USA...

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