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Lecture notes

Lecture notes

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Lecture notes for the Behaviour of Biomolecules module (Year 1 of Biomedical Sciences undergraduate degree at University of Southampton) Professor Tew and Professor Declan Doyle and Dr. Ramon Rios

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  • November 7, 2023
  • 4
  • 2017/2018
  • Lecture notes
  • Professor twes, declan doyle, dr. ramon rios
  • All classes

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Lectures 3 and 4 DD.

Recap.




Stereochemistry.

- Stedman’s three-point fit model (1933) to explain the differential pharmacological
activity of drug enantiomers.
- Describes 3 simultaneous non-covalent bonding interactions and two simultaneous
non-covalent bonding interactions. Alternative interactions can take place but only
with two sites at a time.
- The 2 enantiomers of DCPG have different activities on different receptors. In this
case, in a model system, the combination of the 2 enantiomers had better anti-
epileptic activity as compared to each enantiomer.
- Plasma concentration of S-ibuprofen is lower in patients with liver cirrhosis probably
due to stereospecific clearance in 1st pass metabolism.

Conformational changes upon drug binding.

→ law of mass action assumes there are no conformational changes in the protein upon
ligand binding.
→ many target proteins undergo conformation changes upon drug binding.
→ ATP is bound to the kinase domain of the EGF receptor.
→ kinases transmit signals by attaching phosphate groups to specific sequences on their
target proteins. Hence, kinases have 2 binding events (binding of ATP; binding of target
protein to be phosphorylated).

Induced fit = the interaction of a drug can lock a protein into a conformational state that may
not normally be populated, i.e., rare but does exist.

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