TY - JOUR
T1 - NMR studies of flexible opiate conformations at monoclonal antibody binding sites I. transferred nuclear overhauser effects show bound conformations
AU - Glasel, Jay A.
AU - Borer, Philip N.
N1 - Funding Information:
spectrometer was purchased through grants from the Division of Research Resources of
Funding Information:
J.A.G.; NIH grant GM-32691 to P.N.B. and NIH RR-01317 to George C. Levy and P.N.B. We
Funding Information:
This work was supported by: NIH grant NS-15700 and NSF grant DMB-8519568 to
Funding Information:
Mellon University, Pittsburgh, PA (supported by Division of Research Resources, NIH,
PY - 1986/12/30
Y1 - 1986/12/30
N2 - 500 MHz H, homonuclear, intra-molecular, transferred Nuclear Overhauser Effect measurements have been performed on the bound forms of a classical opiate antagonist, nalorphine and an agonist, levorphanol at their respective binding sites in two different specific anti-opiate monoclonal antibody fragments. Based upon previous studies of opiate conformations in solution the results clearly show without extensive interpretation that one of these flexible haptens has the opposite (from solution) isomeric conformation in its bound form. For nalorphine the axial isomer of the N-allyl substituent is the bound form whereas in solution the equatorial isomer dominates at a ratio of 5:1. For levorphanol the bound form is that of equatorial N-methyl in accord with the low energy conformation in solution. In this preliminary report we discuss the initial measurements and results and their implications with respect to the conformations of flexible ligands at macromolecular binding sites including opiate receptors.
AB - 500 MHz H, homonuclear, intra-molecular, transferred Nuclear Overhauser Effect measurements have been performed on the bound forms of a classical opiate antagonist, nalorphine and an agonist, levorphanol at their respective binding sites in two different specific anti-opiate monoclonal antibody fragments. Based upon previous studies of opiate conformations in solution the results clearly show without extensive interpretation that one of these flexible haptens has the opposite (from solution) isomeric conformation in its bound form. For nalorphine the axial isomer of the N-allyl substituent is the bound form whereas in solution the equatorial isomer dominates at a ratio of 5:1. For levorphanol the bound form is that of equatorial N-methyl in accord with the low energy conformation in solution. In this preliminary report we discuss the initial measurements and results and their implications with respect to the conformations of flexible ligands at macromolecular binding sites including opiate receptors.
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U2 - 10.1016/S0006-291X(86)80182-6
DO - 10.1016/S0006-291X(86)80182-6
M3 - Article
C2 - 3814123
AN - SCOPUS:0022896186
SN - 0006-291X
VL - 141
SP - 1267
EP - 1273
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -