DRUG TARGETS

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

They do so by enclosing the polar molecule in

a hydrophilic cavity
Carrier Protein Blockers
Carrier proteins blockers are drugs that either
bind to carrier protein and prevent it from
accepting its natural guest, or compete with
the natural guest for transport into the cell

Drugs such as the tricyclic antidepressants,

cocaine and amphetamine hinder the uptake
of important neurotransmitters from nerve
synapses, resulting in increased
neurotransmission
Drugs smuggling
Some polar drugs can be smuggled across
cell membranes by carrier proteins if the drug
is attached to a natural guest molecule
LIPIDS
Cell membranes
Cell membranes act as hydrophobic barriers
to the flow of ions, water, and polar
molecules, and also maintain a concentration
gradient for these species
General anasthetics
General anasthetics are fat soluble molecules
that can dissolve in cell membranes and may
produce general anasthesia by affecting the
fluidity of the cell membrane
Tunnelers and smugglers
Various antibacterial an antifungal agents can
build tunnels through cell membranes or act
as ion carriers.
In both cases, normal concentration gradient
are disrupted leading to cell death
Lipid carriers
The lipid carrier involved in carrying building
block for bacterial cell wall synthesis across
the cell membrane is the target for
vancomycin
CARBOHYDRATES
Structure and function

Cell surface carbohydrates are promising

drug targets for the future
Cell surface carbohydrates are conjugated to
proteins or lipid, which act as an anchor in the
cell membrane. The carbohydrate act as a
fingerprint for the cell
Cell surface carbohydrates are crucial to cell
recognition, communication, and adhesion
Antitumor agent
Cell surface carbohydrates present on tumor
cell could act as targets for monoclonal
antibodies if they are unique to the tumor cell
Infection
Bacteria and viruses recognize Cell surface
carbohydrates on host cells which lead to
adhesion then infection.
Inhibition of the process could lead to new
therapies for infection
Inflammation
Cell surface carbohydrates are implicated in
the cell adhesion processes by which
leucocytes adhere to platelets and the wall of
blood vessels prior to exiting the blood vessel.
Inhibition of the process could result in the
new therapies for thrombosis and arthritis
Contraception
New contraceptives could be designed to
prevent cellular recognition between sperm
cells and egg cells.