Peptoids properties

Initial studies on short peptoid oligomers have revealed relatively poor pharmacokinetic properties [18, 79]. Despite the numerous advantageous attributes of peptoids in vitro, there are currently no peptoid-based therapeutics. However, a more thorough exploration of peptoid sequences may reveal species with more appropri-... 

As defined above, peptoids are peptides in which the side chains are transposed from the backbone C -atom to the amide N-atom. In other words, peptoids are peptides composed of N-monosubstituted glycine units, i. e., N-substituted polyglycine chains. These structural changes have a number of consequences for properties of peptoids relative to peptides [185] [229] ... 

Because of this principal structural divergence from coded peptides, peptoids lack amide protons. This property precludes the formation of the intramolecular H-bonds that contribute largely to the stabilization of the most common helical structures of a-peptides. Unlike that of a-peptides, the peptoid backbone is inherently achiral (as it is based on Gly residues). However, it has been reported that sufficient bias to form stable helices of a specific screw sense can be provided by side chains with an a-chiral carbon atom (that is linked directly to nitrogen) (32, 33). The extraordinary resistance of these helices to loss of their ordered secondary structure is another intriguing property of peptoid molecules. 

In addition to these naturally occurring peptides, genetic screens have found new activating peptides, many that have similarities with natural activator peptides (33, 153). Peptoids with regulatory properties that can function in intact cells also have been identified (154) (Fig. 5c). 

The major difference between peptides and peptoids lies in the fact that the side chain substituents R -R in peptoids are attached to the amide nitrogens, thus avoiding the chiral a-centres of a peptide. There are no NH-bonds present in peptoids which has major implications on solubility, cell penetration properties and on the overall conformations which differ significantly from those of peptides. In addition, compared to peptides, peptoids show an increased protease stability due to the tertiary amide bond. 

The example in Figure 2 illustrates these steps for creating a five-dimensional property space from a set of 721 amine-derived peptoid side chains. 

An early demonstration of the proteotytic resistance of pep-toids as well as their initial invention and development within a pharmaceutical/biotechnology company has biased the bulk of the applications of peptoids in a biomedical direction. Several recent reviews cover the biomedical applications of peptoids, but the discussion below focuses on applications where peptoids compete with traditional polymers in the application or are used to mimic biological peptides whose function is dictated by their general chemical properties, such as charge and hydrophobidty (Section 9.15.4). 

One of the most mature applications of peptoids that takes advantage of their general polymer properties is the transfection of cells with nucleic adds. Zuckermann and coworkers utilized hoth rationally designed and lihrary-derived cationic peptoids with and without long aliphatic tails to transfect a DNA plasmid encoding for firefly ludferase into... 

The Ugi-4CR is one of the most versatile tools for the construction of scaffolds with biological properties, such as diazepines [44] and peptoids or peptide-peptoid backbones [45]. hi this context, the group of Andrade has prepared functionalized peptoids by combining methyl isocyanoace-tate, paraformaldehyde, Al-Cbz-glycine, and different primary amines (Scheme 7.17) [45c]. This procedure allowed the synthesis of several peptoids 41 in high yields (78-92%) and... 

Flower plots are particularly useful in assessing the distribution of properties across a collection of compounds. Figure 5 shows the structures and associated flower plots of 18 side-chains from a biased /((-substituted glycine peptoid combinatorial library. The structures on the first row are tyramine... 

Peptoids are oligomers of N-substituted glycines [1]. They are mimics of a-peptides in which the side chains are attached to the backbone iN -amide nitrogen instead of the C"-atom (Fig. 1). Peptoids are achiral, and adopt different conformations from peptides however, they retain the same overall properties of peptides [2], Peptoids hold promise as therapeutics since they often retain the biological activity of the parent peptide and are stable to proteases [3]. 

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