Conformational properties of 2,3-methanopyroglutamic acid in peptides: NMR and x-ray diffraction studies.
The effects of replacing L-pyroglutamic acid with the cyclopropane analogue 2,3-methanopyroglutamic acid (2,3-MeGlp) on conformation and enzymatic stability have been investigated in 2,3-MeGlp-NHMe and the novel thyrotropin releasing hormone (TRH) analogue [2,3-MeGlp1]-TRH by x-ray diffraction and nmr. While 2,3-MeGlp-NHMe adopts a folded conformation (small psi angle) in the solid state, several conformations are available to the molecule in solution. 1H-nmr of the diastereomeric mixture [(+/- )-2,3-MeGlp1]-TRH indicates a close orientation of the pyrrolidone and imidazole rings. The 2,3-MeGlp-His amide bond is considerably more stable to pyroglutamate aminopeptidase than the Glp-His bond in TRH.
Mapelli
C
C
Elrod
L F
LF
Switzer
F L
FL
Stammer
C H
CH
Holt
E M
EM
D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011487:Protein Conformation; D011760:Pyrrolidinones / Q000031:analogs & derivatives / Q000138:chemical synthesis; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D014961:X-Ray Diffraction
D011760:Pyrrolidinones; C059749:2,3-methanopyroglutamic acid; C059750:thyrotropin-releasing hormone, 1-(methano-Glp(2,3))-; D013973:Thyrotropin-Releasing Hormone; D011761:Pyrrolidonecarboxylic Acid