Drug-target Bonds

• PEPTIDE BONDS = the basic chemical bond that holds amino acids together
• PHARMACOPHORE = the minimum set of chemical features a drug must have in order to its target protein
• COVALENT BOND = a strong bond in which atoms share electrons. It is uncommon in drug-target interactions
• IONIC BONDS = an interaction between a cation and an anion
• DIPOLE = a molecule in which the electrons are unevenly distributed, resulting in one part of the molecule having a slight positive charge and another with a slight negative charge
• HYDROGEN BOND = an interaction between a hydrogen covalently bonded to an electronegative atom such as nitrogen
• HYDROGEN BOND ACCEPTORS = the electronegative atom that supplies the lone pair in a hydrogen bond
• HYDROGEN BOND DONOR = the electronegative atom that supplies the hydrogen in a hydrogen bond
• HYDROPHOBIC BOND = a weak interaction between two hydrophobic molecules. It arises due to gain in entropy
• VAN DER WAALS FORCES = weak intersections between dipoles
• CHEMICAL NATURE OF PROTEINS

  • all chiral amino acids that are found in proteins are L-form
  • non-proteinogenic amino acids: important amino acids not found in proteins, e.g. GABA

  
• BINDING DOMAINS

  • PHARMACOPHERE = the minimum set of structural features that a molecule must possess to fit into a target's binding domain
  • BINDING DOMAIN = the 3D arrangement of functional groups
• COVALENT BONDS

  • share outer shell valence electrons
  • covalent bonds range between 200 and 800 KJ/mol
  • usually irreversible, so not common to find them in drug-target interactions

  --> except for phenoxybenzamine and aspirin
• IONIC BONDS

  • charge-charge interactions between an anion and a cation
  • in biological systems:

  -COOH --> -COO-(minus) + H+

  -CNH2 + H+ --> -CNH3+

  • irreversible- but quite strong
  • cations can interact with the electron clouds of aromatic rings in amino acids (called a cation-pi interactions)
• HYDROGEN BONDS

  • the more electronegative atom will take more than its fair share of electrons

  -->oxygen > nitrogen > sulphur = carbon > hydrogen

  • hydrogen bonding involves two electronegative atoms 'sharing' a hydrogen
  • requires

  1. electronegative atom with lone pair(s)
  2. electronegative atom covalently bound to hydrogen

  • moderately strong (2-30 KJ/mol) but are highly directional - have to be in a straight line to have full strength
• HYDROGEN BONDS cont.

  • compounds with more than 10 potential H bond donors and acceptors tend to make poor drugs

  -->because they are too polar to pass through

  membranes but also because they cannot make

  interactions with a range of biological molecules

  • groups can be donors, acceptors, or both

  -->sulphur acts as an acceptor and SH groups as donors

  -->however, it forms much weaker hydrogen bonds than

  nitrogen and oxygen

  
• VAN DER WAALS: permanent dipoles

  • a collection of weak forces that occur between dipoles

  1. the dipoles are permanent
  2. instantaneous dipoles
  3. induced dipoles

  -->can influence the distribution of electrons on a

  neighbouring molecule and cause a complementary

  dipole

  -->these dipoles can interact with each other

  • very weak bonds (0.4-4 KJ/mol); and very numerous
  • strongly dependent on distance (too close = repel) (too far apart = little interaction)