Biomedical subjects

David Papapostolou

Publications and source records attributed to David Papapostolou.

3 recordsLinked to original sources

PubMed2006

Development of lipopeptides for inhibiting 20S proteasomes.

Proteasomes are responsible for the cytoplasmic turnover of the vast majority of proteins including regulatory proteins. We have synthesized lipopeptides a new class of non-covalent inhibitors of the 20S proteasome and assayed their inhibitory capacities. Their ability to inhibit at micromolar concentrations chymotrypsin-like and post-acid activities depends on peptide length (3 or 6 amino acids), sequence (presence of a positively or negatively charged amino acid), and alkyl chain length (C6-C18). These structural features could be varied to selectively inhibit one or more of the three proteasome activities.

Amino Acid Sequence↗

PubMed2004

[Proteasome and proteolysis].

The maintenance of cellular homeostasis and the ability of cells to respond to their environment depend on the degradation of bulk proteins and orderly degradation of key regulatory proteins and their inhibitors. The 26S proteasome plays an essential role in these degradations. It is involved in the activation and inactivation of many cellular processes such as cell cycle progression, apoptosis and regulation of gene expression. It presents unique structural and functional properties. It degrades proteins by an unusual mechanism. Several series of proteasome inhibitors have been developed, useful to elucidate the biological roles of this multicatalytic enzyme. Velcade (bortezomid) was the first proteasome inhibitor to undergo, in may 2003, clinical trials in cancer patients.

Aging↗

PubMed2002

Regulation of the 26S proteasome activities by peptides mimicking cleavage products.

The implication of the released peptides in allosteric effects during protein degradation catalyzed by the proteasome is an important question not completely resolved. We present here data showing modulation of 26S proteasome activities by peptides composed of 5 or 6 natural amino acids that mimic the products generated during protein breakdown. Several of these peptides inhibit the chymotrypsin-like activity of the Xenope 26S proteasome whereas its trypsin-like activity is enhanced. The basic peptides produced competitive inhibition of the chymotrypsin-like activity and the acidic peptides, parabolic inhibition involving two different binding sites. Our results are in agreement with a model involving hypothetical non-catalytic sites interacting with effectors to modulate the peptidase activities of the proteasome. They also suggest that allosteric effects may occur in the proteasome during protein degradation.

Animals↗