one amino and one carboxylic acid group, the pI can be calculated from the
pK a values of this molecule.
pI ¼
pK a1 þ pK a2
2
For amino acids with more than two ionizable groups, e.g. lysine, the same
formula is used but the two pK a values used are those of the two groups that
lose and gain a charge from the neutral form of the amino acid.
The process that separates proteins according to their isoelectric point is
called isoelectric focusing. At a pH below the pI proteins carry a net positive
charge, whereas above the pI they carry a net negative charge. Appling this
principle, gel electrophoretic methods have been developed to separate
proteins. The pH of an electrophoretic gel is determined by the buffer used
for that gel. If the pH of the buffer is above the pI of the protein being run,
the protein will migrate to the positive pole (negative charge is attracted to a
positive pole). Similarly, if the pH of the buffer is below the pI of the protein
being run, the protein will migrate to the negative pole of the gel (positive
charge is attracted to the negative pole). If the protein is run with a buffer pH
that is equal to the pI, it will not migrate at all. This also applies for
individual amino acids.
4.10 Importance of functional groups in determining
drug actions and toxicity
In Chapter 2, you have already learned that most drugs bind to the
appropriate receptor molecules to exhibit their pharmacological actions,
and also toxicity, which in fact is the adverse pharmacological action. A
drug’s pharmacological activity is inherently related to its chemical structure. Various functional groups present in the drug molecules are involved in
the drug–receptor binding or interaction. For example, drugs containing
hydroxyl or amino groups tend to be involved in hydrogen bonding with the
receptor.
Any changes in the functional groups in a drug molecule can render
significant changes in the activity and toxicity, and this is the basis of any
structure–activity-relationship (SAR) study of drug molecules. The SAR
study is the study for understanding the relationship of chemical structure to
activity. The activity can be a pharmacological response, binding, toxicity or
any other quantifiable event. In SAR studies, essential functional groups or
structural features of a drug molecule, which are responsible for the
optimum pharmacological actions with minimum toxicity index, are identified or optimized. These essential functional groups for the pharmacological
activities are called pharmacophores.
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CH4 ORGANIC FUNCTIONAL GROUPS
pK a values of this molecule.
pI ¼
pK a1 þ pK a2
2
For amino acids with more than two ionizable groups, e.g. lysine, the same
formula is used but the two pK a values used are those of the two groups that
lose and gain a charge from the neutral form of the amino acid.
The process that separates proteins according to their isoelectric point is
called isoelectric focusing. At a pH below the pI proteins carry a net positive
charge, whereas above the pI they carry a net negative charge. Appling this
principle, gel electrophoretic methods have been developed to separate
proteins. The pH of an electrophoretic gel is determined by the buffer used
for that gel. If the pH of the buffer is above the pI of the protein being run,
the protein will migrate to the positive pole (negative charge is attracted to a
positive pole). Similarly, if the pH of the buffer is below the pI of the protein
being run, the protein will migrate to the negative pole of the gel (positive
charge is attracted to the negative pole). If the protein is run with a buffer pH
that is equal to the pI, it will not migrate at all. This also applies for
individual amino acids.
4.10 Importance of functional groups in determining
drug actions and toxicity
In Chapter 2, you have already learned that most drugs bind to the
appropriate receptor molecules to exhibit their pharmacological actions,
and also toxicity, which in fact is the adverse pharmacological action. A
drug’s pharmacological activity is inherently related to its chemical structure. Various functional groups present in the drug molecules are involved in
the drug–receptor binding or interaction. For example, drugs containing
hydroxyl or amino groups tend to be involved in hydrogen bonding with the
receptor.
Any changes in the functional groups in a drug molecule can render
significant changes in the activity and toxicity, and this is the basis of any
structure–activity-relationship (SAR) study of drug molecules. The SAR
study is the study for understanding the relationship of chemical structure to
activity. The activity can be a pharmacological response, binding, toxicity or
any other quantifiable event. In SAR studies, essential functional groups or
structural features of a drug molecule, which are responsible for the
optimum pharmacological actions with minimum toxicity index, are identified or optimized. These essential functional groups for the pharmacological
activities are called pharmacophores.
184
CH4 ORGANIC FUNCTIONAL GROUPS