DRUG TARGETS / DRUG RECEPTORS

Followings are the drug targets

 ENZYMES
 RECEPTORS
 CARRIER PROTEINS
 STRUCTURAL PROTEINS
 NUCLEIC ACIDS
 LIPIDS
 CARBOHYDRATES
presented by:
Dr Farooq saleem

1-STRUCTURAL PROTEINS

• Structural proteins are not usually drug targets.

• Example:
• a protein called tubulin,which can polymerize into small tubes called
microtubules.These microtubules have various cellular functions which are
important to the structural integrity and motality of the cells.
• Microtubules are also important for cell division
• At the time of division these polymerizes to form spindle fibers,which pushes two
daughter cells apart and chromosomes are transferred to each daughter cell
Drugs Acting On Microtubules:
 Drugs which inhibit depolymerization and repolymerization of microtubules inhibits
cell division and potentially useful in the treatment of cancer.
• Example:
 Vincristine
 Taxol

2-NUCLEIC ACIDS

 Nucleic acids are the drug atrgets for various important drugs such as anti-microbial
and anti-cancer agents.
 TYPES OF NUCLEIC ACIDS:
• 1.DNA
 gentic blue print for the cell and essential for biosynthesis of proteins
 Consist of two polymeric oligonucleoside strands,which forms double helix
 Each strand of the helix is made up of a deoxyribose sugar-phosphate backbone ,a
nucleic acid base is linked to each sugar moeity
 The double helix is held together by hydrogen bonding
 Adenine(A) pairs with Thymine(T),while guanine(G) pairs with cytocine(C)
  One DNA strand is complemmentary to each other and responsible for transfer of
genetic information from cell to cell
 Each DNA strand can act as a template for the synthesis of two DNA molecules
 Nucleotide bases and the order in which they occur determine the genetic code
2.RNA
 It is a single polymer and does not form a double helix

TYPES
 mRNA
 rRNA
 tRNA
 All these are required for the biosynthesis of proteins.
 mRNA acts as a photocopy of specific region of DNA and carries genetic code for a
specific protein.
 rRNA attacks to one end of the mRNA molecule and travel along the length of the
strand.
 Nucleic acid bases on mRNA read as triplets
 tRNA recognizes these triplets. Protein is constructed on tRNA and transferred from
one tRNA to next tRNA untill the full protein has been completed.
 1.DNA INTERCALATORS
 Interclating drugs binds to DNA by inserting themselves b/w the stacked base pairs
 Intercalation distort the DNA double helix and prevent DNA from being copied,thus
blocking protein synthesis.
• Example :
• Anti-bacterials
• Anti-cancer agents
 On order to slip b/w the stacked bases the drug must be planner and have the
correct dimension
 It must be hydrophoic
 Tricyclic system is the correct size to be inserted and can interact with nucleic acid
bases by van der waal interactions
 Proflavine also contain amino groups that form ionic bond with phosphate groups on
the DNA backbone thus strengthening the bonding interactions
 Some intercalators are present in the grooves that are present in the DNA helix
 There are two different grooves in DNA
 One minor groove and one major groove
 Dimemsions of these grooves are important for many drugs
• 2.ALKYLATING AGENT:
• These contain an electrophile functional group such as alkyl halide.
• Reaction of an Alkyl halide with a nucleophilic group on DNA (e.g N-atoms on
guanine unit) results in a nucleophilic substitution reaction where a
nucleophile displaces the halide and forms a covalent bond with drug.
• If there are two electrophile groups are present in the drug ,the reaction occurs
twice resulting in cross linking with in a strand or b/w the strands. This way
cross linking disrupt the normal function of the DNA.
 • Example: Uracil Mustard

3.CHAIN CUTTERS
4.ANTI_SENSE THERAPY
5.INHIBITION OF RIBOSOMAL RNA
3-LIPIDS
1.Cell membrane:
 Cell membrane consist of phospholipid bilayer,which acts as a hydrophobic barriers.
 Water and ions can only cross this layer through ion channels which are controlled
by receptors
Polar molecules cross using carrier proteins
 Concentration gradient
 Cell membrane acts as barrier to drugs that are intended to act on a target within a
cell.
 Drug must be hydrophobic in order to cross the lipid bilayer of cell membrane.
2.General anesthetics :
 General anesthetics disrupt the cell membrane structure,making it more fluid.
 Receptor protein may be involved
3.Tunnelers and Smugglers :
Compounds that disrupt the cell membrane structure can be devastating.
Example:
 Various antifungal and anti-bacterials destroy the cell by building helical
structures through the cell membrane ,thus forming a tunnel through which
ions and small polar molecules can flow in an unanihillated manner.
4.Lipid carriers:
These are not major drug targets.
Example:Vancomycin acts on lipid carriers in bacteria which are responsible for building
blocks required for the synthesis of cell membrane
4-CARBOHYDRATES
Introduction:
 These are generally neglected as drug targets.however,these may be important
targets for future
Structure:
 Cell surface carbohydrates are known as glycoconjugates since carbohydrates
arelinked to a protein pr lipidthat are embedded in the cell membrane
 Protein or lipid acts as anchor for carbohydrates,which sticks out from the surface of
the cell to act as “finger print” from the cell
 Cell surface carbohydrates are crucial to cell recognition and communication.
  They are important to several adhesive processes, whereby a cell stick to the other
cell.
 Cell surface carbohydrates could be the potential drug targets for a number of
diseases including cancer, stroke,arthritics genetic disease etc.

Example :
1- Anti tumor agents:
 It has been observed that the cell surface carbohydrates present on the tumor cells
are different in structure and composition from those which are normally present in
healthy cells.
 Such carbohydrates act as antigen so, it should be possible to produced monoclonal
antibodies which will recognized and bind to them, thus directing the immune
system against the tumor.
2-Infection
 Cell surfaces glycoproteins are important to the mechanism involved in infection.
 Portions on the surface on the bacteria and viruses recognized particular
carbohydrates on the host cells initiating the process of infection, If this recognition
and adherence process could be inhibited.
 Then new anti-bacterial and anti-viral drugs could be designed.