Jl. Flippenanderson et al., X-RAY STRUCTURE OF TYR-D-TIC-PHE-PHE-NH2 (D-TIPP-NH2), A HIGHLY POTENT MU-RECEPTOR SELECTIVE OPIOID AGONIST, The journal of peptide research, 49(5), 1997, pp. 384-393
Tyr-D-Tic-Phe-Phe-NH2 (D-TIPP), a linear tetrapeptide containing the c
onformationally restricted Tic residue (tetrahydroisoquinoline-3-carbo
xylic acid), is an opioid agonist which exhibits high affinity and sel
ectivity for the mu-receptor. Its conformational features have been st
udied using a combination of solid-state (X-ray) and modeling (molecul
ar mechanics and Monte Carlo simulations) methods. The results of the
X-ray study showed two distinct conformers for D-TIPP, with the main d
ifferences lying in the orientation of the Tyr side-chain and the pres
ence of both D-Tic(+) and D-Tic(-) conformations for the D-Tic residue
. The peptide backbone is folded and stablized hi; the formation of on
e intramolecular hydrogen bond. The modeling results also indicated a
folded backbone for the peptide and both cis and trans conformers for
the D-Tic residue an found in the Lowest-energy structures. Comparison
of the X-ray and modeling results shows many similarities especially
around the D-Tic residue. (C) Munksgaard 1997.