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Helix‐Forming Oligoureas: Temperature‐Dependent NMR, Structure Determination, and Circular Dichroism of a Nonamer with Functionalized Side Chains
Author(s) -
Hemmerlin Christine,
Marraud Michel,
Rognan Didier,
Graff Roland,
Semetey Vincent,
Briand JeanPaul,
Guichard Gilles
Publication year - 2002
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(200211)85:11<3692::aid-hlca3692>3.0.co;2-w
Subject(s) - chemistry , circular dichroism , oligomer , side chain , moiety , pyridine , monomer , stereochemistry , crystallography , proton nmr , helix (gastropod) , cotton effect , nuclear magnetic resonance spectroscopy , peptide , two dimensional nuclear magnetic resonance spectroscopy , polymer , polymer chemistry , organic chemistry , ecology , biochemistry , snail , biology
To further investigate the degree of structural homology between γ ‐peptides A and N , N′ ‐linked oligoureas B , we prepared oligourea nonamer 2 containing Ala, Val, Leu, Phe, Tyr and Lys side chains. Oligomer 2 was synthesized on solid support from activated monomers, i.e. , from enantiomerically pure succinimidyl {2‐{[(9 H ‐fluoren‐9‐ylmethoxy)carbonyl]amino}ethyl}carbamates 3a – f that are further substituted at C(2) of the ethyl moiety. These precursors were conveniently prepared from N ‐Fmoc‐protected β 3 ‐amino acids with corresponding side chains. Detailed NMR studies (DQF‐COSY, TOCSY, and ROESY) in (D 5 )pyridine revealed that 2 adopts a regular ( P )‐ 2.5 helical secondary structure very similar to that previously determined for oligourea heptamer 1 and closely related to the ( P )‐ 2.6 14 helix of γ ‐peptides. Temperature‐dependent NMR further demonstrated the conformational homogeneity and remarkable stability of the structure of 2 in pyridine. The CD spectrum of 2 (0.2 m M ) was recorded in MeOH with the aim to gain more information about the conformation of oligoureas. In contrast to 2.6 ‐helical γ ‐peptides, which display only a weak or no Cotton effect, oligourea 2 exhibits an intense positive Cotton effect at ca. 203 nm ([ Θ ]=+373000 deg cm 2 dmol −1 ) that decreases only slowly upon increasing the temperature.