Drug Target
Drug Target
Drug Target
DRUG TARGETS
ENZYMES
RECEPTORS / MEMBRANE RECEPTORS
CARRIER PROTEINS
LIPIDS
CARBOHYDRATES
STRUCTURAL PROTEINS
NUCLEI ACIDS
ENZYMES
ENZYMES
Enzymes are proteins that catalyze the
bodys chemical reactions.
The starting material for an enzyme-
catalyzed reaction is known as a
substrate
ACTIVE SITE
The active site is a hollow or cleft on the
enzyme surface where the substrate
binds and the reaction take place
The substrate is bound to the active site
by intermolecular interactions
The active site contains amino acid
residues, which act as nucleophiles or
acid/base catalysts in the reaction
mechanism
MECHANISM OF CATALYSIS
Serine and cysteine can act as
nucleophiles in a reaction mechanism,
while histidine can act as an acid/base
catalyst
Substrate binding weakens important
bonds and constrains the substrate in a
specific conformation such that it will
undergo reaction
ENZYME INHIBITORS
Competitive inhibitors are compete with
the natural substrate for the active site.
Noncompetitive inhibitors bind to
allosteric binding site and distort the
active site so that it can no longer bind
the natural substrate
Reversible inhibitors bind by
noncovalent interactions, whereas
irreversible inhibitors are linked to
enzyme through covalent bonds
ENZYME SELECTIVITY
Drug should be as selective as possible
for the target enzyme or isozyme.
RECEPTORS
RECEPTORS
Most receptors are proteins that traverse the
cell membrane with a binding site on the
extracellular region
Binding of a chemical messenger causes the
receptor to change shape, initiating a process
that result in a message being receive by the
cell
The messenger does not undergo any
reaction and departs unchanged, allowing the
receptor to reform it original shape
CHEMICAL MESSENGER
Chemical messenger are neurotransmitters or
hormones
Neurotrasmitters are released by nerves to
interact with specific target cells and are short
lived
Hormone are released by glands and travel
round the body to interact with all the
receptors that recognize them
BINDING SITE
The binding site of a receptor is the
equivalent of an enzymes active site, but has
no catalytic activity.
RECEPTOR TYPES
Different receptors have different binding sites
and interact with different chemical
messengers
Each receptor can exist as various types and
subtypes, which vary in concentration
between different organs and tissues
This allow design of drugs that are tissue
selective
AGONIST AND ANTAGONIST
Agonist mimic a receptors chemical
messenger
Antagonist bind to a receptor but do not
activate it
By binding to the receptor, they prevent
activation by natural messenger
SIDE EFFECTS
Side effects arise if a drug interacts with more
than one receptor type or subtype
MEMBRANE BOUND RECEPTOR
FAMILIES
There are three families of membrane
bound receptors
Ligand-gated ion channel receptors
G-protein-coupled receptors
Tyrosine kinase-linked receptors
LIGAND-GATED ION CHANNEL
Ligand-gated ion channel receptors are part
of a protein complex called an ion channel
When ligand binds to the receptor, the
resulting induced fit causes the ion channel to
open, allowing ions to flow through the
channel for as long as the messenger bound
G-PROTEIN-COUPLED RECEPTOR
G-protein-coupled receptor activate signal
proteins that called G proteins
The G protein fragments to release a subunit,
which binds to adenylate cyclase
The enzyme is activated or deactivated
depending on the nature of original G protein,
and catalyzes the conversion of ATP to
cAPM, which act as a secondary messenger
and initiate a signaling cascade within the cell
TYROSINE KINASE LINKED
RECEPTOR
Are proteins that act both as receptor and
enzyme
Binding of a chemical messenger activates a
kinase enzyme on the intracellular region of
the protein, resulting in the phosphorylation of
tyrosine residues
These regions act as binding sites for signal
proteins and enzyme, initiating a signaling
cascade which results in gene expression and
protein synthesis
INTRACELLULAR RECEPTOR
Some receptors are present within the cell
and so the chemical messenger must
hydrophobic to cross the cell membrane
Activation of the estrogen receptor leads to a
receptor-ligand comlex, which enters the
nucleus and switches on transcription, leading
to the synthesis of protein
CARRIER PROTEINS
Function
Carrier proteins transport important polar
molecules across the cell membrane