Peptoids mimetics

Scheme 63 Comparison of (A) Glycopeptide and Glycopeptoid, (B) a Typical Asparagine-Linked iV-Acet-ylglucosaminide and its N-Linked Peptoid Mimetic, and (C) a Typical f3-D-Xylose-(l—>3)-Ser Linkage and its Homoserine Glycopeptidomimetic 485 4891...

As such, the magainins provide a useful initial target for peptoid-based peptido-mimetic efforts. Since the helical structure and sequence patterning of these peptides seem primarily responsible for their antibacterial activity and specificity, it is conceivable that an appropriately designed, non-peptide helix should be capable of these same activities. As previously described (Section 1.6.2), peptoids have been shown to form remarkably stable hehces, with physical characterishcs similar to those of peptide polyprohne type-I hehces (e.g. cis-amide bonds, three residues per helical turn, and 6A pitch). A faciaUy amphipathic peptoid helix design, based on the magainin structural motif, would therefore incorporate cationic residues, hydrophobic aromatic residues, and hydrophobic aliphathic residues with threefold sequence periodicity. 

Tab. 1.3 Magainin-mimetic peptoid sequences, and antibacterial and hemolytic activities...

In summary, these recently obtained results demonstrate that certain amphi-pathic peptoid sequences designed to mimic both the helical structure and approximate length of magainin helices are also capable of selective and biomimetic antibacterial activity. These antibacterial peptoids are helical in both aqueous buffer and in the presence of lipid vesicles. Ineffective (non-antibacterial) peptoids exhibit weak, random coil-like CD, with no spectral intensification in the presence of lipid vesicles. Selective peptoids exhibit stronger CD signals in bacterial-mimetic vesicles than in mammalian-mimetic vesicles. Non-selective peptoids exhibit intensely helical CD in both types of vesicles. 

K.M., Griesser, H.J., Kwak, J., Goodman, M., and Steele, J.G. Peptoid-con-taining collagen mimetics with cell binding activity. J. Biomed. Mater. Res. 2000,... 

The oligomeric peptidomimetics such as peptoids are particularly interesting compounds since they provide access to an enormous molecular diversity by variation of the building blocks. Peptoids represent a class of polymers that are not found in nature. They differ from the peptides in the manner of side-chain attachment and thus can be considered as peptide mimetics in which the side chain has been shifted from the chiral a-carbon atom in a peptide to the achiral... 

O-o-V"1 gA° R X.H.C R 0 NH2 [52] Amides of different types are produced to form peptido-mimetics and/or peptoids. Not only condensation reactions but also alkylation and substitution reactions are described. Resins/linkers used Wang, Rink amide, Knorr TenlaGel. Phosphoramides were prepared on Pore glass, 3 split-pool libraries. [21] [50-57]... 

Fig. 13 Stabilized helices and nonnatural helix mimetics several strategies that stabilize the a-helical conformation in peptides or mimic this domain with nonnatural scaffolds have been described. Recent advances include [1-peptide helices, terphenyl helix-mimetics, mini-proteins, peptoid helices, side-chain crosslinked a-helices, and the hydrogen bond surrogate (HBS) derived a-helices. Circles represent amino acid side-chain functionality (Reprinted from Henchey et al. [52], Copyright (2008) with permission from Elsevier)...

Using the solid-phase strategy also libraries of other biopolymer mimetics have become accessible, for example, oligoureas, oligo-sulfones, peptidosulfonamides, [14] peptido-phosphoramidates, and peptoids (Scheme 2). 

Quaternary Structure Mimetics and Self-Assembly of Peptoids. 406... 

Schmitt, J., Bernd, M., Kutscher, B., and Kessler, H. (1998) Synthesis of dolastatin 15 mimetic peptoids. Bioorg. Med. Chem. Lett., 8, 385-388. 

---