TY - JOUR
T1 - Effects of Thionation and Fluorination on Cis-Trans Isomerization in Tertiary Amides
T2 - An Investigation of N-Alkylglycine (Peptoid) Rotamers
AU - Engel-Andreasen, Jens
AU - Wich, Kathrine
AU - Laursen, Jonas Striegler
AU - Harris, Pernille
AU - Olsen, Christian A
PY - 2015/6/5
Y1 - 2015/6/5
N2 - Peptoids constitute a class of peptidomimetics with potential as protease resistant, biologically active ligands. To harness the full potential of such compounds, however, detailed predictive insight into their propensity to adopt well-defined secondary structures is highly desirable. In this work we present an investigation of the effects of thioamides and/or fluorides in peptoid monomer model systems using chemical synthesis, NMR spectroscopy, and X-ray crystallography. We find that the steric environment surrounding the tertiary amide bonds is the key promoter of conformational preference, and X-ray crystallographic interrogation of our model systems did not suggest the presence of stabilizing n → π∗ interactions unless the carbonyls were altered electronically by α-halogenation or thioamide formation. In addition to the function as an investigative tool, these two types of modification may thus be utilized as stabilizers of secondary structure in future oligomer designs, such as the cis-amide-based polypeptoid helices that resemble the polyproline type-I helix.
AB - Peptoids constitute a class of peptidomimetics with potential as protease resistant, biologically active ligands. To harness the full potential of such compounds, however, detailed predictive insight into their propensity to adopt well-defined secondary structures is highly desirable. In this work we present an investigation of the effects of thioamides and/or fluorides in peptoid monomer model systems using chemical synthesis, NMR spectroscopy, and X-ray crystallography. We find that the steric environment surrounding the tertiary amide bonds is the key promoter of conformational preference, and X-ray crystallographic interrogation of our model systems did not suggest the presence of stabilizing n → π∗ interactions unless the carbonyls were altered electronically by α-halogenation or thioamide formation. In addition to the function as an investigative tool, these two types of modification may thus be utilized as stabilizers of secondary structure in future oligomer designs, such as the cis-amide-based polypeptoid helices that resemble the polyproline type-I helix.
U2 - 10.1021/acs.joc.5b00048
DO - 10.1021/acs.joc.5b00048
M3 - Journal article
C2 - 25738410
SN - 0022-3263
VL - 80
SP - 5415
EP - 5427
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 11
ER -