No abstract

Deltorphins A, B, and C exhibit high delta-affinities (Ki = 0.12-0.31 nM) and very high delta-receptor binding selectivities (Ki mu/Ki delta = 1800-4100). A study of the delta-receptor binding properties of 15 deltorphin analogues focused primarily on the influence of the anionic group in the C-terminal tetrapeptide. Amidation of the beta-carboxyl groups of [Asp7], [Glu4], or [Asp4] in deltorphins A, B, and C, respectively, yielded peptides with enhanced mu-receptor affinities and minor changes in delta-affinities (Ki delta = 0.20-0.65 nM), but 5-8-fold diminished delta-selectivities. A free C-terminal carboxyl group markedly reduced delta-affinities and decreased delta-selectivities 6-11-fold; thus, the C-terminal amide group critically facilitates delta-affinity. Modifications in the anionic charged group or hydrophobic residues in the C-terminal tetrapeptide address domain of deltorphin A altered spatial distributions critical for delta-affinity and selectivity; e.g., [Nle6]deltorphin A enhanced mu-affinity and lowered delta-selectivity by two-thirds; the progressive, step-wise repositioning of Asp in deltorphin C (from position 4 to 7) was accompanied by linear decreases in delta-affinities and -selectivities, and increased mu-affinities of these peptides; enhancement of the charge density to -2, in [Asp6, Asp-OH7]deltorphin A, decreased delta-affinity and -selectivity, while [Asp4,5,His7]deltorphin A bound to neither mu- nor delta-sites. These results demonstrate that while an anionic group may occasionally facilitate high delta-receptor affinity, it represents an absolute requirement for the high delta-binding selectivity of these peptides. The locations of the charged groups relative to hydrophobic residues in the address domain of the peptide are also critical determinants for both delta-affinity and -selectivity.

Summary Cutaneous and bronchial immediate allergic reactivity and the serum level of IgE specific for each of four common inhalant allergens were determined for 153 asthmatic patients. Positive bronchial reactivity to an extract was not detected in any of the patients with a negative prick test reaction to that extract but did occur in 9% of the patients in whom the serum tests results for IgE specific to that allergen fell within the range regarded as negative. Highly significant correlation coefficients between the degree of bronchial and cutaneous allergic reactivity to the allergen extracts were found and these were slightly but significantly less than the correlation between the serum level of allergen specific IgE and the degree of bronchial allergic reactivity to the allergen extracts. These findings indicate that the results both of prick testing with appropriate extracts and estimation of the serum level of allergen specific IgE can be used to predict not only the presence of detectable bronchial reactivity to inhalant allergens but also the degree of this reactivity. However, for the routine investigation of asthmatic patients measurement of the serum level of allergen specific IgE would appear to have little advantage over properly performed prick tests.