ISSN:
1573-3904
Keywords:
Opioid peptide
;
X-ray diffraction
;
Peptide conformation
;
Antagonist
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Summary The solid state structures of two synthetic opioid peptides have been determined by X-ray single crystal analysis. The first X-ray structure is that of N,N-diallyl-(O-t-butyl)-Tyr-Aib-Aib-Phe-Leu-OMe (RTI02), a protected derivative of the δ-receptor selective antagonist ICI 174,864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH. ICI 174,864 is one of a series of rationally designed Aib-substituted enkephalin analogs which have shown site-specific antagonist properties. The second compound, the tetrapeptide Tyr-Tic-Phe-Phe-OH (TIPP), is one of a family of linear peptides containing the conformationally restricted Tic residue (tetrahydroisoquinoline-3-carboxylic acid). TIPP exhibits high affinity, selectivity and antagonism for the δ-receptor. Crystals of both peptides were obtained by slow evaporation and found to be monoclinic in space group P21. Unit cell dimensions for RTI02 were: a=13.619(4) Å, b=12.467(3) Å, c=13.750(4) Å, β=96.03(4)o and V=2322(1) Å3. The asymmetric unit contained one molecule of RTI02 and one molecule of methanol, giving a calculated density of 1.156 g cm-3. Unit cell dimensions for TIPP were: a=8.879(5) Å, b=20.146(8) Å, c=12.710(6) Å, β=107.89(2)o and V=2164(2) Å3. The asymmetric unit contained one molecule of TIPP and three molecules of acetic acid, giving a calculated density of 1.251 g cm-3. The RTI02 backbone has a double β-bend, stabilized by two intramolecular hydrogen bonds. The TIPP backbone is also folded, but with only a single bend, stabilized by one intramolecular hydrogen bond and several hydrogen bonds to solvent molecules. Both compounds contain aromatic rings in close vicinity (4–6 Å).
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00128528
