Peptoid

Peptoids are an archetypal and relatively conservative example of a peptidomimetic oligomer (Tab. 1.1). In fact, the sequence of atoms along the peptoid backbone is identical to that of peptides. However, peptoids differ from peptides in the marmer of side chain appendage. Specifically, the side chains of peptoid oligo-... 

I 7 Versatile Oligo(N-Substituted) Glycines The Many Roles of Peptoids in Drug Discovery Tab. 1.1 Comparison of key characteristics of peptides and peptoids... 

Fig. 1.1 Comparison of the primary structure of peptide and peptoid oligomers...

Like peptide oligomers, peptoids can be analyzed by HPLC and by mass spectrometry. They can be sequenced by Fdman degradation [13] or by tandem mass spectrometry [14] since, like polypeptides, they conveniently fragment along the main chain amides [15, 16]. 

Drug Discovery via Smaii-Moiecuie Peptoid Libraries... 

Because of their ease of synthesis and their structural similarity to peptides, many laboratories have used peptoids as the basis for combinatorial drug discovery. Peptoids were among the first non-natural compounds used to establish the basic principles and practical methods of combinatorial discovery [17]. Typically, diverse libraries of relatively short peptoids (< 10 residues) are synthesized by the mix-and-split method and then screened for biological activity. Individual active compounds can then be identified by iterative re-synthesis, sequencing of compounds on individual beads, or indirect deduction by the preparation of positional scanning libraries. 

Peptoid hbraries have also yielded compounds active in the disruption of RNA-protein interactions. Compounds not derived from library syntheses are discussed in Section 1.4.1. A peptoid 9-mer with a number of cationic groups was discovered (Fig. 1.4) after several rounds of mixture deconvolution, that was able to block the interaction of HIV-1 Tat protein with TAR RNA at nanomolar concentra-... 

Drug Discovery via Small-Molecule Peptoid Libraries I 7... 

Fig. 1.3 Various small-molecule peptoid ligands derived from combinatorial libraries...

Fig. 1.4 Structure of a peptoid/peptide hybrid that is a submicromoiar inhibitor of the HIV-1 Tat/Tar interaction...

Peptoid-Based Drug Delivery and Molecular Transporters Cellular Uptake... 

Recently, there has been significant interest in peptidomimetic forms of Tat49 57, not only because of its membrane translocation activity, but as a means of treating HIV infection [1]. Several peptoids, similar in sequence to Tat49 57, have been synthesized with the intention of preventing the HlV-Tat/Tar interaction, and thus preventing HIV replication [24, 25, 30, 31]. However, only recently has this class of peptoids been applied to membrane translocation and dmg delivery applications. 

Peptoids have also shown great utility in their ability to complex with and deliver nucleic acids to cells, a critical step toward the development of antisense drugs, DNA vaccines, or gene-based therapeutics. Most non-viral nucleic acid delivery systems are based on cationic molecules that can form complexes with the polyan-... 

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. 

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