Dove e quando
2017-07-03 | Aula magna DCCI
Il Prof. Jason K. Sello, della Brown University, Providence, RI (USA),
il 3 luglio 2017, alle 15.00, terrà, presso il Dipartimento di Chimica e Chimica
Industriale, in aula magna, un seminario dal titolo "Novel Small Molecules,
Targets, and Strategies in Anti-Infective Development"
Abstract:
The increasing number of infections caused by multi-drug resistant bacteria
portends a public health crisis. Unfortunately, therapeutic options are
limited because of a long innovation gap in the last half-century of
antibacterial drug development. The gap is reflected in marketed drugs that
have closely related structures and act on a few essential phenomena like
DNA replication, transcription, translation, and cell envelope homeostasis.
This situation is problematic because genetic mutations or genes that confer
resistance to one antibacterial drug often compromise the efficacies of
others with the same target or mechanism of action. To circumvent this
“cross-resistance”, we must identify and validate new antibacterial drug
targets. Among the most compelling of today’s antibacterial drug targets are
the chaperone-dependent proteases that are known to play critical roles in
bacterial physiology and pathogenicity. Interestingly, the accumulation of
data that have validated these enzymes as drug targets has been coincident
with discoveries of novel small molecules that critically perturb them. This
seminar will describe efforts in the Sello group to discover, design, and
synthesize small molecules that lethally perturb the structures and
functions of enzymes that mediate protein homeostasis in a variety of
pathogenic bacteria. Additionally, efforts to develop inhibitors of
chaperone-dependent proteases for applications in cancer therapy will be
discussed.