Library Generation Analysis and Combinatorial Chemistry: dedicated to Bruce Merrifield 1 Bruce Merrifield Dynamic Combinatorial Assembly of Peptide-Rhenium Coordinates: Application to the Selection of hCyp-18 inhibitors from a Library of 12 × 16 Components 3 Dynamic Combinatorial Assembly of Peptide-Rhenium Coordinates: Coordination Chemistry for Generating New Analogs of hCyp-18 Ligands 5 Oxor...

i The thesis entitled “Uses of Pyrrole Amino Acid based Scaffolds in Peptidomimetics and Studies Directed Towards the Total Synthesis of Antascomicin A”, consists of three chapters: CHAPTER I: Deals with the synthesis and conformational studies of pyrrole amino acid based peptidomimetics. This chapter is divided into two parts: Part A: Describes the synthesis and conformational studies of linea...

On the basis of the structure of the CVIM tetrapeptide substrate of mammalian protein farnesyltransferase, a series of imidazole-containing peptidomimetics was designed and synthesized, and their inhibition activity against Trypanosoma brucei protein farnesyltransferase (TbPFT) was evaluated. Peptidomimetics where the 5-position of the imidazole ring was linked to the hydrophobic scaffold showe...

Recently, western countries have recorded a decrease in the death rate imputed to AIDS. This success has been largely attributed to the presence on the market of chemotherapies that inhibit the infectivity of the predominant causative agent, the HIV-1 virus, by targeting essential viral enzymes. One of these is the protease (HIV-1 PR) whose activity is a prerequisite for viral replication. Two ...

Signal Transducer and Activator of Transcription (STAT) proteins are a family of cytoplasmic transcription factors consisting of 7 members, STAT1 to STAT6, including STAT5a and STAT5b. STAT proteins are thought to be ideal targets for anti-cancer therapy since cancer cells are more dependent on the STAT activity than their normal counterparts. Inhibitors targeting STAT3 and STAT5 have been deve...

New peptidomimetics containing a β2,2-isoxazoline amino acid, 5-(aminomethyl)-3-phenyl-4,5-dihydroisoxazole-5-carboxylic acid (Isox-β2,2AA), were prepared and studied by NMR theoretical calculations. Interestingly, inserting R-Isox-β2,2AA in short tri- hexapeptide models, an unexpected α-turn-like motif was observed, thanks to unprecedented strong H-bond involving C=N of isoxazoline side chain ...

Gamma-secretase, exhibiting characteristics of aspartyl protease, mediates the intramembranous proteolysis of beta-amyloid precursor protein (APP) and Notch, and it is considered to be a prime pharmacological target in the development of therapeutics for Alzheimer's disease (AD). To identify compounds that block gamma-secretase-mediated proteolysis, we used a highly sensitive cell-based reporte...

The amide moiety of peptides can be replaced for example by a triazole moiety, which is considered to be bioisosteric. Therefore, the carbonyl moiety of an amino acid has to be replaced by an alkyne in order to provide a precursor of such peptidomimetics. As most amino acids have a chiral center at Cα, such amide bond surrogates need a chiral moiety. Here the asymmetric synthesis of a set of 24...

Antibacterial drugs with novel scaffolds and new mechanisms of action are desperately needed to address the growing problem of antibiotic resistance. The periplasmic oxidative folding system in Gram-negative bacteria represents a possible target for anti-virulence antibacterials. By targeting virulence rather than viability, development of resistance and side effects (through killing host nativ...