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Solid-phase peptide synthesis and circular dichroism study of chiral β-peptoid homooligomers

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Summary.

N-alkyl-β-alanine oligomers (β-peptoids) with α-chiral side chains [(R)- or (S)-1-(phenylethyl)amino groups] were synthesized and analyzed by CD spectroscopy. These chiral β-peptoid homomers exhibited chain-length-dependent and solvent-dependent ellipticity, strongly indicating the presence of a secondary structure in solution. The CD behaviour was only slightly temperature-dependent upon heating, as also previously observed for stable α-peptoid helices containing the same type of side chains. Thus, the data presented here comprise the first evidence for a chain length-dependent secondary folding of compounds with this novel peptidomimetic backbone design. In addition, applicability of a novel hyphenated technique, HPLC-SPE-NMR/MS, for analysis of crude SPPS reaction products was demonstrated.

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Abbreviations

β-Nrpe:

(R)-N-(1-phenylethyl)-β-alanine

β-Nspe:

(S)-N-(1-phenylethyl)-β-alanine

CD:

circular dichroism

DMF:

N,N-dimethylformamide

HRMS:

high-resolution mass spectrometry

MRE:

mean residue ellipticity

PyBOP® :

benzotriazol-1-yl-oxy-tris(pyrrolidino)phosphonium hexafluorophosphate

RP-HPLC:

reversed-phase high performance liquid chromatography

SPE:

solid-phase extraction

SPPS:

solid-phase peptide synthesis

TFA:

trifluoroacetic acid

TFE:

2,2,2-trifluoroethanol

TFFH:

fluoro-N,N,N,N-tetramethylformamidinium hexafluorophosphate

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Authors’ address: Dr. C. A. Olsen, Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark; Present address: The Scripps Research Institute

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Olsen, C., Lambert, M., Witt, M. et al. Solid-phase peptide synthesis and circular dichroism study of chiral β-peptoid homooligomers. Amino Acids 34, 465–471 (2008). https://doi.org/10.1007/s00726-007-0546-8

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  • DOI: https://doi.org/10.1007/s00726-007-0546-8

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