Pi system

Abstract: The substituent effect of the dihydro[60]fullerenyl group and its hydrophobic parameters have been evaluated quantitatively. The substituent constant has been determined from the pK value of a fullerene-based, para-substituted benzoic acid 1 in 80% dioxane/water (v/v) by NMR spectroscopy. The resulting Hammett sigma value of 0.06, consistent with a small electron-withdrawing effect of C(60), is a consequence of the fact that only inductive effects can be transmitted through the two tetracoordinate carbon atoms between the fullerene pi system and the para-position of the benzoic acid moiety in 1. The parameter pi, which describes the hydrophobic character of the substituent C(60), has been evaluated as the difference between that of 1 and model compound 2. The pi value, which is larger than 3, indicates that the fullerene cage imparts high hydrophobicity to the molecule to which it is attached. Finally, we have evaluated how the fullerene spheroid influences the acid-base properties and nucleophilicity of the pyrrolidine nitrogen in a suitably functionalized fulleropyrrolidine. The fulleropyrrolidine 4 (pK(BD)(+)=5.6) is six orders of magnitude less basic and 1000 times less reactive than its model 3 (pK(BD)(+)=11.6). This may be related to through-space interactions of the nitrogen lone pair and the fullerene pi system.

Abstract: The phenotypes of the protease inhibitor (PI) alpha-1-antitrypsin have been analyzed by isoelectric focusing on polyacrylamide gels. With improved resolution by a modified procedure it was possible to demonstrate a fifth PI*M suballele. The bands of PI M5 are located between PI M1 and PI M3. In addition, a further deficiency allele similar to PI*Z was found in a female patient with obstructive pulmonary disease. This variant was provisionally named PI Zaugsburg (PI Zaug). Family data confirm a simple codominant mode of inheritance for PI Zaug.

Abstract: Alphal-antitrypsin is a glycoprotein synthesized mostly in the liver; it is also produced by macrophages and by the epithelial cells lining the intestinal wall. It is the major inhibitor of leukocytic elastase and plays a crucial role in protecting pulmonary tissue from elastolytic destruction: its congenital deficiency is associated with a high risk of pulmonary emphysema. Through mechanisms not yet fully understood, alphal antitrypsin deficiency is also associated with chronic liver disease and a rare form of panniculitis (1). Alphal antitrypsin is a glycoprotein composed of a chain of 394 amino acids, with three carbohydrate chains linked to three different amino acids (Asn“, Asn”, The three carbohydrate chains are composed of N-acetylglucosamine, mannose, galactose and sialic acid, arranged in two or three antennae. The carbohydrate chains are arranged in a heterogeneous pattern and this pattern is responsible for the electrophoretic heterogeneity of the two major alphal-antitrypsin bands, when serum is migrated in isoelectric focusing. Mature alpha,-antitrypsin has a globular configuration (of 6.7 nm by 3.2 nm) with carbohydrate chains radiating from the surface of one end of the molecule. Inside, the protein is arranged in an alpha helix and in beta-pleated sheets. The first 20 N-terminal amino acids are an exception to this configuration and they can be cleaved. The various points at which this cleavage occurs contribute to the electrophoretic heterogeneity of the molecule. An important part of the protein structure are the salt bridges ( G l ~ ’ ~ ~ L y s * ~ ~ and G l ~ ~ ~ ~ L y s ~ ~ ’ ) : when they are not formed (in the Z pathological variant) the protein cannot be secreted properly and accumulates in the cisterna of the rough endoplasmic reticulum (2, 3). The active site of alphal-antitrypsin is located between Met35s Ser359 and forms a kind of hook that protrudes from the surface of the molecule. This structure has a high affinity for the active site of neutrophil elastase (structured like a pocket) and a noncovalent bond forms between the two molecules. This interaction is suicidal for both molecules, and the complex alphal-antitrypsin-neutrophilic elastase is quickly phagocytosed by macrophages. The association rate in normal conditions was estimated to be lo7 MI s-’ s; the dissociation rate, by contrast, is slower, with a Ki of M. These characteristics render alpha,-antitrypsin the most efficient among the numerous elastase inhibitors (4). The normal serum level of alphal-antitrypsin ranges from 150 to 350 mg/dl with a half-life of 3-5 days. The serum level varies greatly according to certain physiological states, such as pregnancy, pathological conditions such as acute inflammations and during estrogen and progesterone therapy. The distribution of the protein in the tissues is not uniform; it is reduced to 10% in the fluid of the lower respiratory tract and this explains why patients with deficiency of the protein have an extremely low level of the protein in alveolar fluid.