MEDICINAL CHEMISTRY:-

RECEPTORS:-
• these are specialized, membrane-bound proteins
• they receive (bind to) external stimuli
• thus they effectively serve as signal transducer
• upon receiving external signal, they undergo structural changes
• this ultimate trigger various cellular activities
Receptor proteins can be classified by their location. Transmembrane
receptors include ion channel-linked (ionotropic) receptors, G protein-linked
(metabotropic) hormone receptors, and enzyme-linked hormone receptors
Each receptor is linked to a specific cellular biochemical pathway. While
numerous receptors are found in most cells, each receptor will only bind
with ligands of a particular structure, much like how locks will only accept
specifically shaped keys. When a ligand binds to its corresponding
receptor, it activates or inhibits the receptor's associated biochemical
pathway.

Ligand:-
In biochemistry, a ligand is any molecule or atom which binds reversibly to a
protein. A ligand can be an individual atom or ion. It can also be a larger and
more complex molecule made from many atoms. A ligand can be natural, as an
organic or inorganic molecule. A ligand can also be made synthetically, in the
laboratory. This is because the key properties of a ligand are found in its
chemical structure. If that structure can be recreated in the laboratory, the
synthetic ligand will be able to interact in the same ways a natural ligand acts.
Types of Receptors:-
There are two classification of receptors
According to their location
According to their binding with molecules
1.Internal receptors:-
Internal receptors, also known as intracellular or cytoplasmic receptors, are
found in the cytoplasm of the cell and respond to hydrophobic ligand
molecules that are able to travel across the plasma membrane. Once
inside the cell, many of these molecules bind to proteins that act as
regulators of mRNA synthesis to mediate gene expression. Gene
expression is the cellular process of transforming the information in a cell’s
DNA into a sequence of amino acids that ultimately forms a protein. When
the ligand binds to the internal receptor, a conformational change exposes
a DNA-binding site on the protein. The ligand-receptor complex moves into
the nucleus, binds to specific regulatory regions of the chromosomal DNA,
and promotes the initiation of transcription. Internal receptors can directly
influence gene expression without having to pass the signal on to other
receptors or messengers.
2. Extra cellular receptors:-
Extracellular receptors are cell surface receptors binds to an external ligand
molecule and convert an extracellular signal into intracellular signal
There are mainly 3 general categories of cell surface receptors:-
3. Ion Channel-Linked Receptors:-
Ion channel-linked receptors bind a ligand and open a channel through the
membrane that allows specific ions to pass through. To form a channel, this
type of cell-surface receptor has an extensive membrane-spanning region.
In order to interact with the phospholipid fatty acid tails that form the center
of the plasma membrane, many of the amino acids in the membrane-
spanning region are hydrophobic in nature. Conversely, the amino acids
that line the inside of the channel are hydrophilic to allow for the passage of
water or ions. When a ligand binds to the extracellular region of the
channel, there is a conformational change in the protein’s structure that
allows ions such as sodium, calcium, magnesium, and hydrogen to pass
through.
4. G-Protein Linked Receptors:-
G-protein-linked receptors bind a ligand and activate a membrane protein
called a G-protein. The activated G-protein then interacts with either an ion
channel or an enzyme in the membrane. All G-protein-linked receptors
have seven transmembrane domains, but each receptor has its own
specific extracellular domain and G-protein-binding site.
Cell signaling using G-protein-linked receptors occurs as a cyclic series of
events. Before the ligand binds, the inactive G-protein can bind to a newly-
revealed site on the receptor specific for its binding. Once the G-protein
binds to the receptor, the resultant shape change activates the G-protein,
which releases GDP and picks up GTP. The subunits of the G-protein then
split into the α subunit and the β subunit. One or both of these G-protein
fragments may be able to activate other proteins as a result. Later, the GTP
on the active α subunit of the G-protein is hydrolyzed to GDP and the β
subunit is deactivated. The subunits reassociate to form the inactive G-
protein, and the cycle starts over.
5. Enzyme-Linked Receptors:-
Enzyme-linked receptors are cell-surface receptors with
intracellular domains that are associated with an enzyme. In some
cases, the intracellular domain of the receptor itself is an enzyme
or the enzyme-linked receptor has an intracellular domain that
interacts directly with an enzyme. The enzyme-linked receptors
normally have large extracellular and intracellular domains, but
the membrane-spanning region consists of a single alpha-helical
region of the peptide strand. When a ligand binds to the
extracellular domain, a signal is transferred through the
membrane and activates the enzyme, which sets off a chain of
events within the cell that eventually leads to a response. An
example of this type of enzyme-linked receptor is the tyrosine
kinase receptor. The tyrosine kinase receptor transfers phosphate
groups to tyrosine molecules. Signaling molecules bind to the
extracellular domain of two nearby tyrosine kinase receptors,
which then dimerize. Phosphates are then added to tyrosine
residues on the intracellular domain of the receptors and can then
transmit the signal to the next messenger within the cytoplasm.
GENERAL PROPERTIES OF RECEPTORS:-
All sensory receptors are transducers
Transducer is any device that converts one form of energy to another

1. Recognition:-
2. TRANSDUCTION:-
The receptor protein must exist in a conformational state that allow for
recognition and binding of a compound and must satisfy the following criteria

 SATURABILITY:-
it means receptor exist in infinite number
 REVERSIBILITY:-
Binding must occur non-covelently due to reinter
molecular forces
 AGONIST SPECIFICITY:-
Structurally related drugs should bind while physically disimillar
compound should bind poorly
 TISSUE SPECIFICITY:-
Binding should occur in a tissue known to be sensitive to the
endogeneous ligand
 STEREO SELECTIVITY:-
Receptor should recognize only one of the naturally occurring
optical isomers
FUNCTIONS OF RECEPTORS:-
1. To correctly recognise (bind) the ligand (primary message)
2. To correctly respond to that ligand (usually by changing shape)
3. To transmit the signal to the inside of the cell across the cell
membrane
4. To stop transmitting the signal once the ligand has left the
receptor (this bit is often missed out)