Requirements for high affinity binding of glycine analogs to the glycine site of the NMDA receptor complex
Correlation of the isopotential contours of the optimized conformations of a series of alpha-amino acids, in their neutral and zwitterionic forms, with their potencies to inhibit [3H]glycine binding and to enhance [3H]10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine ([3H]MK-801) binding, leads to the following conclusions: (a) steric congestion at the amino group is detrimental to binding potency; (b) a zwitterionic amino acid is required for high affinity to the receptor; (c) a conformation in which the carboxylate group is at a 90 degrees dihedral angle to the ammonium nitrogen is preferred for high affinity; and (d) placing the carbon backbone of the zwitterionic alpha-amino acid, in its preferred conformation, above the plane defined by the ammonium nitrogen and the carboxylate oxygen atoms, and viewing the molecule along the nitrogen to carboxylate carbon axis, there is a space forbidden to the ligand (receptor-required-space) to the left
Lewin, A., Skolnick, P., Marvizon, J. C., Paul, I. A., & Bowen, J. P. (1993). Requirements for high affinity binding of glycine analogs to the glycine site of the NMDA receptor complex. European Journal of Pharmacology, 247(1), 1-10.