Peptoids sequencing

Figs. 1.6 and 1.7). This type of CD spectrum is observed for certain heterooligomeric peptoid sequences with as few as 33% chiral aromatic residues, in both aqueous and polar organic solvent (acetonitrile, methanol). 

A peptoid pentamer of five poro-substituted (S)-N-(l-phenylethyl)glycine monomers, which exhibits the characteristic a-helix-like CD spectrum described above, was further analyzed by 2D-NMR [42]. Although this pentamer has a dynamic structure and adopts a family of conformations in methanol solution, 50-60% of the population exists as a right-handed helical conformer, containing all cis-amide bonds (in agreement with modeling studies [3]), with about three residues per turn and a pitch of 6 A. Minor families of conformational isomers arise from cis/trans-amide bond isomerization. Since many peptoid sequences with chiral aromatic side chains share similar CD characteristics with this helical pentamer, the type of CD spectrum described above can be considered to be indicative of the formation of this class of peptoid helix in general. 

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. 

Improve Understanding of Peptoid Sequence/Structure Relationships... 

Translate Bioactive Peptide Sequences into Bioactive Peptoid Sequences... 

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-... 

Scheme 7.S Construction of peptoid sequences. Cleavage was carried out using trifluoroacetic acid (TFA) at room temperature.

Peptoids [22] form a particular promising class of oligomeric peptidomimetics, which consists of A-substituted-glycine derivatives. Thus, the concepts to translate a particular peptide sequence, in this case CAAX to a corresponding peptoid sequence is a perfectly suitable approach to obtain potential famesyl inhibitors. This approach was adopted by... 

In a third study, Czyzewski et designed a library of 26 different peptoid sequence variants of peptoid 1 (Figure 15). 

Fig. 10 (a) Using molecular dynamics, protein-like peptoid sequences were obtained by iterative process of globule formation and addition/redistribution of polar residues on the globule surface, (b) Globule-to-coil transition was induced by titration with acetonitrile, which leads to unfolding of the globules, (c) The transition is more pronounced and sharper in the case of the protein-like sequence. Reproduced from [93], with permission from American Oiemical Society... 

Fig. 11 Library design for 15-mer amphiphilic peptoid sequences with green non-ionic hydrophiiic residues, blue ionic hydrophiiic residues, riodicity ...

Research continues into new and. specialized chemical representations. At the level of indexes, the venerable concept of molecular ID numbers has re.surfaced as a critical component in a 3D chemical diversity partitioning scheme, in addition, hierarchical fragment indexes have been implemented with a tremendous enhancement in search performance. The primary driver for the introduction of new representations is the recent focus on the needs of combinatorial chemistry for library design, specification, storage and retrieval. Noteworthy examples are CHUCKLES and CHORTLES, both extensions of SMILES the former supports the representation of peptide and peptoid sequences on both the monomer and atomic levels, and the latter allows the representation of mixtures as simple strings of characters. 

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