L108- Enzymes as drug targets Flashcards
what are protease ?
are enzymes that hydrolyse the amide bond in the polypeptide structures of proteins.
what are the biological roles or proteases?
- breakdown of the protein content of food
- blood coagulation cascade
- activation of messenger proteins and peptides
- vital role in bacteria, fungi and plants
what kind of binding does protease-substrate have?
very specific
what are the names of non-peptide drugs that mimic the action of peptides/proteins?
peptidomimetics
what are the advantages of peptidomimetics?
orally active: increased bioavailability
increased stability to digestive and metabolic enzymes reduced antigenicity
reduced manufacturing costs (chemical synthesis!)
what needs to be done in order to convert a peptide into a peptidomimetic?
bioisosteric replacement of the peptide link (A)
replacement of a natural amino acid with a non-natural one (B)
replacement of natural L-amino acids with their D-enantiomers (C)
how does changing steroconfiguration affect bonding or hydrolysis?
-the molecule needs to twist in a certain way. It may twist to bind or fit in the active site but not be able to be hydrolysed now
what is HIV?
is the causative agent of AIDS
why are they called Serine-, Threonine, Cysteine-proteases?
These protease names refer to the key “nucleophilic” active site amino acid that is involved in amide bond cleavage
how do covalent inhibitors of Serine-, Threonine, Cysteine-proteases?
Place an electrophilic group in close proximity to the active site nucleophile
what is Metallo-proteases?
utilise an enzyme-bound metal ion (usually Zn2+) to facilitate amide bond hydrolysis
What is a Potent Metallo-protease inhibitors?
can be designed by including metal- binding functional groups in the inhibitor structure
