Premium
Alkylation of γ‐Azaproline Creates Conformationally Adaptable Proline Derivatives for pH‐Responsive Collagen Triple Helices
Author(s) -
Aronoff Matthew R.,
Egli Jasmine,
Schmitt Adeline,
Wennemers Helma
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201905768
Subject(s) - stereocenter , steric effects , chemistry , alkylation , proline , stereochemistry , ring (chemistry) , triple helix , nitrogen inversion , cyclic peptide , amino acid , peptide , nitrogen , organic chemistry , enantioselective synthesis , biochemistry , catalysis
C γ ‐substituted proline derivatives are valuable tools for developing functionalized collagen peptides for biological and materials investigations, yet the stereochemistry at C γ can produce undesired steric or stereoelectronic constraints. Alkylated γ‐azaproline (γ‐azPro) derivatives are proline mimetics that lack a stereogenic center at the γ‐position of the ring and can thus utilize the invertibility of nitrogen to adapt their conformation. NMR spectroscopic analyses and DFT calculations highlighted how alkylated γ‐azPro derivatives are conformationally dynamic and adopt conformational preferences through ring pucker flip along with nitrogen inversion. Lastly, incorporation of alkylated γ‐azPro into collagen peptides produced functionalized pH‐responsive triple helices with similar thermal stabilities, regardless of their placement in the Xaa or Yaa position within the characteristic Xaa‐Yaa‐Gly repeating unit of collagen peptides.