Anders Undén

Interleukin-1 in adrenal chromaffin cells

Interleukin-1, first identified as a macrophage factor of importance in infections and inflammation, is a protein with properties of an endogenous pyrogene and lymphocyte activating factor. Occurrence of interleukin-1-like immunoreactivity was demonstrated in the noradrenergic chromaffin cells of the rat and mouse adrenal gland by means of two antisera raised against synthetic peptides corresponding to the amino acid sequences 169-194 and 201-215 of the murine interleukin-1 precursor protein. These antisera also inhibited stimulation of interleukin-2 receptor expression by purified human interleukin-1. Reserpine, which is known to deplete catecholamines, also caused release of the interleukin-1-like immunoreactive material. The interleukin-1 content of the rat adrenal medulla was estimated by radioimmunoassay, and if released the adrenal interleukin-1 pool may result in plasma interleukin-1 levels of about 10(-12). The interleukin-1-immunoreactive material obtained from the rat adrenal gland was characterized as a trypsin-sensitive protein with a molecular weight in the range of 13,000-19,000. This protein fraction stimulated interleukin-2 receptor expression on human T-cells as earlier shown for interleukin-1.

Regulation of neuropeptide Y (NPY) binding by guanine nucleotides in the rat cerebral cortex

In the presence of GTP, GDP, GMPP(NH)P, GMPP(CH2)P, GMPP(S)P but not in the presence of GMP, cGMP or ATP, the high affinity binding of neuropeptide Y (NPY) was reduced in a dose‐dependent manner. GTP (0.1 mM) diminished the maximal binding capacity for 125I‐labelled NPY by 40% without any change in the equilibrium dissociation constant of the receptor 125I‐labelled NPY complex.

Solid phase synthesis of 1,2,3,4-tetrahydro-β-carbolines; implications for combinatorial chemistry

Abstract A general method for the solid phase synthesis of tetrahydro-β-carbolines is described. Resin bound tryptophan residues or non-peptide structures carrying 3-(2-aminoethyl)indole structures react rapidly under mild reaction conditions and in high yields with aldehydes to produce C-l substituted 1,2,3,4-tetrahydro-β-carbolines in a Pictet-Spengler reaction. The method can be employed to readily produce a wide range of tetrahydro-β-carbolines in combinatorial chemistry.

Solid-phase synthesis of peptide aminoalkylamides using an allyl linker

Abstract The synthesis of an allylic linker is presented to which primary and secondary amino groups can be anchored on solid phase. By acylating MBHA resin with allyl linker HOCH 2 CHCHCH 2 OCH 2 COOH followed by treatment with 4-nitrophenyl chloroformate a mixed carbonate linker is obtained to which amino groups can be attached. The allyl carbamate linkage is stable to both bases and anhydrous acids and can be cleaved by palladium-catalysed allyl transfer under mild reaction conditions.

A NEW PROTECTING GROUP FOR ASPARTIC ACID THAT MINIMIZES PIPERIDINE-CATALYZED ASPARTIMIDE FORMATION IN FMOC SOLID PHASE PEPTIDE SYNTHESIS

Abstract The β-3-methylpent-3-yl ester of Fmoc aspartic acid, Fmoc-Asp(OMpe)-OH, is presented as a new protecting group for aspartic acid which provides good protection against base-catalyzed aspartimide formation in Fmoc solid phase peptide synthesis.

Postmortem Changes in Binding to the Muscarinic Receptor from Human Cerebral Cortex

Abstract: The effects of storage at 4°C on the antagonist and agonist binding properties of the muscarinic acetyl‐choline receptor from fresh surgical and frozen autopsy samples from human cerebral cortex were studied. The number of 1‐[3H]3‐quinuclidinyl benzilate binding sites and their affinities were stable up to 51 h, both when stored as pieces of intact nonfrozen tissue and as a homogenate. The agonist binding properties as measured by the ability of the muscarinic agonist carbachol to compete with l‐[3H]3‐quinuclidinyl benzilate were also stable up to 51 h when the tissue was stored in the form of pieces. The affinity for carbachol decreased when the tissue was stored as a homogenate. The frozen autopsy samples showed no significant differences in binding properties in comparison with fresh neurosurgical tissue.

Solid-phase synthesis of oxygen-bridged tetrahydropyridones

A solid-phase approach for the synthesis of oxygen-bridged tetrahydropyridones has been developed. A diamine is attached to Trt-Cl resin and condensed with different aliphatic or aromatic ketones a ...

The β-2,4-dimethyl-3-pentyl ester as a new protecting group for aspartic acid that prevents base-catalyzed aspartimide formation in solid phase peptide synthesis

Abstract A new protecting group for aspartic acid that effectively prevents base-catalyzed aspartimide formation is presented. The 2,4-dimethyl-3-pentyl ester is particularly useful in orthogonal peptide synthesis when the removal of base-labile protecting groups is accompanied by aspartimide formation.

Repetitive solid-phase synthesis of polyamines

Abstract A repetitive solid-phase method for the synthesis of polyamines is described. Primary amino groups attached to a crosslinked polystyrene resin are monoalkylated by acid labile, benzhydryl-based alkyl chlorides. Reductive alkylation of the resulting secondary amino group by Fmoc-protected aminoaldehydes gives a N -benzhydryl polyamine backbone. Treatment of the resin with trifluoroacetic acid cleaves both the benzhydryl protective group and the polyamine derivative from the resin. By using benzhydryl protective groups with different acid stability, unbranched, branched and partly branched polyamines are synthesized.

Solid phase synthesis of tropane derivatives

Abstract The azabicyclic moiety present in tropane alkaloids can be conveniently synthesized in high yield on solid phase using a modification of Robinsons tropinone synthesis. 1 The e-amino group on a lysine residue attached to Tentagel ® resin was treated with 10 eq excess of succinic dialdehyde and 1 eq of acetonedicarboxylic acid for 12 hours with a citric acid buffer of pH 4 as solvent, resulting in the formation of an 8-azabicyclo[3.2.1]octane structure on the e-amino group of lysine in 93% yield.