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X-ray structures of the δ opioid antagonist TIPP and a protected derivative of the δ opioid antagonist ICI 174,864

✍ Scribed by Judith L. Flippen-Anderson; Clifford George; Jeffrey R. Deschamps; P. Anantha Reddy; Anita H. Lewin; George A. Brine

Publisher
Springer Netherlands
Year
1994
Tongue
English
Weight
573 KB
Volume
1
Category
Article
ISSN
1573-3149

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✦ Synopsis

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 5-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 8-receptor, Crystals of both peptides were obtained by slow evaporation and found to be monoclinic in space group P2j. Unit cell dimensions for RTI02 were: a = 13.619(4)/~, b = 12.467(3)/~, c = 13.750(4)/~, [3 = 96.03(4) ° and V = 2322(1) A 3. 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) ,~, b = 20.146(8) ,~, c = 12.710(6) ,~, [3 = 107.89(2) ° and V = 2164(2) ,~3 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 [3-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/~).

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