P-Peptoids

In early 1998, a further class of peptoid oligomers appeared [25], when a solid-phase method was developed to synthesize N-substituted P-aminopropionic acid oligomers, termed P-peptoids. Treatment of Wang s resin with acryloyl chloride, followed by Michael addition of primary amines afforded N-substituted P-alanines. A combinatorial library of 

---

Solid-phase synthesis has also been used to make peptoids, some examples of which are shown in Fig. 2.4. Compounds of general structure 2.8, where the amino acid side chain is on the nitrogen, have been prepared either by the corresponding Fmoc-protected N-aUcylated glycines (33) or, in an improved method, via treatment of a resin-bound secondary amine with bromoacetic acid to produce the first peptoid building block, which is then elaborated via iteration of the procedure (34). Other modified P-peptoid structures such as 2.9 with repeating P-amino propionic units have been prepared by acylation of a resin-bound amine with acriloyl chloride followed by Michael addition of a primary amine. The cycle is repeated to build up the polymer... 

Fig. 1.7 Illustration of the distinct CD exhibited by peptoid helices containing solely aromatic or solely aliphatic residues. Sample concentrations were 60 p,M in acetonitrile. Spectra were acquired at room temperature.

R. M.J. Solid-phase syntheses of peptoids using Fmoc-protected N-substituted glycines The synthesis of (retro) peptoids of leu-enkephalin and substance P. Euro. J. Chem. 1998, 4, 1570-1580. 

Wender, P.A., Mitchell, D.J., Pelkey, E.T., Steinman, L., and Rothbard, J.B. Xhe design, synthesis, and evaluation of molecules that enable or enhance cellular uptake Peptoid molecular transporters. Proc. Nad. Acad. Sci. USA 2000, 97, 13003-13008. 

Structures of Peptoids with a,-Adrenergic and p-Opiate Activity (as Reported in ref. 36)... 

This approach gave fair yields of Gly-based building units (R2=H). A similar approach was used 122 to prepare a variety of monomers (Scheme 18) used in the synthesis of Leu-enkephalin peptoids. In the case of substituted a-halocarboxylic acids or esters bearing R2 side chains the yields were lowered because of racemization and p-elimination resulting in the undesired a, 3-dehydrocarboxylic acids in addition to the desired chiral building unit. Another problem was polyalkylation. 

Colburn, W. 1991. Peptide, peptoid, and protein pharmacokinetics/pharmacodynamics. In P. Garzone.W. Colburn, and M. Mokotoff (Eds.), Peptides, peptoids, and proteins. Harvey Whitney Books, Cincinnati, OH, pp. 94-115. 

Statz Andrea R, Park Jong P, Chongsiriwatana Nathaniel P et al. (2008) Surface-immobilised antimicrobial peptoids. Biofouling 24 439 148... 

Versatile oligo (A-substituted) glycines the many roles of peptoids in drug discovery, in Pseudo-Peptides in Drug Development (Neilsen, P. E., ed.), Wiley-VCH, Weinheim, pp. 1-31. 

With these techniques, libraries have been created of many classes of NCEs some of which include peptides, peptoids, prostaglandins, imidazoles, alkaloids, heparins, oxazoles, benzodiazepines, and P-lactams. 

Working, P.K. Cossum, W.A. Clinical and preclinical studies with recombinant human proteins effect of antibody production. In Pharmacokinetics and Pharmacodynamics Peptides, Peptoids and Proteins Garzone, P.D., Colburn, W.A., Mokotoff, M., Eds. Harvey Whitney Books New York, 1991 201-233, Ch. 13. 

A. Chen, D. Baker, B. Ferraiolo, Points to consider in correlating bioassays and immunoassays in the quantitation of peptides and proteins in Peptides, Peptoids, and Proteins (Eds. P. Garzone, W. Colburn, M. Mokotoff), Harvey Whitney Books, Cincinnati, OH, 1991, pp. 54-71. 

Three different types of building block strategies were developed for the efficient synthesis of peptoids as schematically shown in Scheme 2.4.1 (Approaches A-C)P ... 

---