NMR studies of new arginine vasopressin analogs modified with alpha-2-indanylglycine enantiomers at position 2 bound to sodium dodecyl sulfate micelles.
In this paper, we use NMR spectroscopy and molecular modeling to examine four new vasopressin analogs modified with alpha-2-indanylglycine (Igl) at position 2, [L-Igl(2)]AVP (I), [D-Igl(2)]AVP (II), [Mpa(1),L-Igl(2)]AVP (III) and [Mpa(1),D-Igl(2)]AVP (IV), embedded in a sodium dodecyl sulfate (SDS) micelle. All the analogs display antiuterotonic activity. In addition, the analogs with D-Igl reveal antipressor properties. Each analog exhibits the tendency to adopt beta-turns at positions 2, 3 and/or 3, 4, which is characteristic of oxytocin-like peptides. Mutual arrangement of aromatic residues at positions 2 and 3 has been found to be crucial for binding antagonists with the OT and V(1a) receptors. The orientation of the Gln(4) side chain seems to be important for the V(1a) receptor affinity. In each of the peptides studied, the Gln(4) side chain is folded back over the ring moiety. However, it lies on the opposite face of the tocin moiety in analogs with L and D enantiomers of Igl.
Lubecka
Emilia
E
University of Gdańsk, Poland.
Kwiatkowska
Anna
A
Ciarkowski
Jerzy
J
Sikorska
Emilia
E
D001127:Arginine Vasopressin / Q000737:chemistry* / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry; D007189:Indans / Q000737:chemistry*; D008823:Micelles; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry*; D013237:Stereoisomerism
C548312:2-indanylglycine; D007189:Indans; D008823:Micelles; D001127:Arginine Vasopressin; D012967:Sodium Dodecyl Sulfate; D005998:Glycine