Negative cooperativity in the molecular recognition of excitatory amino-acid derivatives by synthetic allosteric 1,1 '-binaphthalene receptors

The optically active allosteric receptors (-)-(R,R)3 and (+)-(R,R)-4 were s ynthesized for the molecular recognition of the N-(benzyloxy)carbonyl (N-Cb z)-protected excitatory amino acids aspartic acid (Asp, 1) and glutamic aci d (Glu, 2). These macrocyclic structures consist of two 1,1'-binaphthalme m oieties connected by two but-2-yne-1.4-diyl (for (-)-(R,R)3) or p-xylylene (for (+)-(R,R)-4) bridges between the O-atoms in the minor grooves. Each 1, 1'-binaphthalene moiety contains two 2-acetamidopyridin-6-yl (CONH(py)) H-b onding sites in the major groove to bind excitatory amino-acid derivatives via two COOH ... CONH(py) H-bonding arrays and additional secondary electro static interactions The formation of stable complexes with 1:2 host-guest s toichiometry was proven by the evaluation of fluorescence binding titration s using a multiple-wavelength nonlinear least-squares curve-fitting procedu re, Job plot analysis, and solubilization experiments. Complexation of the first excitatory amino-acid guest at binding site 1 reduces the affinity fo r the second guest at binding site 2. As measures for the negative cooperat ivity between the two sites. the ratios of the association constants for th e first and second binding events, {K-a(1:1)/K-a(1: 2)}(infinity rr) (corre cted for the statistical preference of the 1:1 complex formation), were fou nd to adapt values between 1.4 and 2.4, and the Hilt coefficients n(H) vari ed between 0.49 and 0.59.