Novel beta-lactam derivatives: potent and selective inhibitors of the chymotrypsin-like activity of the human 20S proteasome.

A series of beta-lactam derivatives has been designed and synthesized to inhibit the chymotrypsin-like activity of the human 20S proteasome. The most potent compounds of this new structural class of beta-subunit selective 20S proteasome inhibitors exhibit IC50 values in the low-nanomolar range and show good selectivity over the trypsin-like and post-glutamyl-peptide hydrolytic activities of the enzyme.

Synthesis of dammarane-type triterpenoids with anti-inflammatory activity in vivo.

The 17-alpha-substituted triterpene 1 [(17alpha)-23-(E)-dammara-20,23-diene-3beta,25-diol] showed promising activity in animal models of immunosuppression and inflammation. Using a mouse model for inflammatory skin diseases (oxazolone-induced allergic contact dermatitis, ACD) as the directing in vivo test system, Structure-activity-relationship studies with the aim to understand the necessary structural requirements for the biological activity of 1 were conducted. Furthermore, we anticipated to identify biologically active compounds with the 17beta configuration, which are thermodynamically more stable and much easier to synthesize.

Sterically congested tripodal phosphites: conformational analysis, solid-state polymorphism, metal complexation, and application to the asymmetric hydrosilation of ketones.

The synthesis as well as isolation and crystallographic analysis of two solid-state polymorphs of the tripodal ligand tri[2,2',2' '-tris[(2,4,8,10-tetrakis(1,1-dimethylethyl)dibenzo[d,f][1,3,2]dioxaphosphepin-6-yl)oxy]ethyl]amine (3) is described. Form I crystallized from ethyl acetate in the space group P2(1)/n with the unit-cell parameters a = 20.070(10) A, b = 17.

Sanglifehrin-cyclophilin interaction: degradation work, synthetic macrocyclic analogues, X-ray crystal structure, and binding data.

Sanglifehrin A (SFA) is a novel immunosuppressive natural product isolated from Streptomyces sp. A92-308110. SFA has a very strong affinity for cyclophilin A (IC(50) = 6.

Argyrins, immunosuppressive cyclic peptides from myxobacteria. II. Structure elucidation and stereochemistry.

The structures of argyrins A-H were elucidated by NMR spectroscopy, chemical degradation and X-ray analysis as cyclic octapeptides. Argyrins A and B, in addition to the common amino acids tryptophan, glycine, dehydroalanine and alanine or alpha-aminobutyric acid, sarcosine, contain 2-(1-aminoethyl)thiazol-4-caboxylic acid and the novel amino acid 4'-methoxytryptophan. In argyrins C and D the latter is replaced by 4'-methoxy 2'-methyltryptophan.