DRUG TARGETS Flashcards
to identify the target, study the ____ of the disease
pathophysiology
The vast majority of drugs used in medicine are targeted to ____, such as receptors, enzymes, and transport proteins.
proteins
it is important to understand ____ in order to understand drug action on proteins.
protein structure
- Most abundant macromolecules
- Perform wide array of functions.
protein
building blocks of proteins
amino acids
For amino acids to polymerized they should form
peptide bonds
PROTEINS
will be functional if they undergo ____
folding process
PROTEIN STRUCTURES OR CONFORMATIONS
Polypeptide chain—proteins are not functional (nascent)
PRIMARY STRUCTURE
PROTEIN STRUCTURES OR CONFORMATIONS
only structure left during denaturation because of peptide bonds
primary structure
PROTEIN STRUCTURES OR CONFORMATIONS
- Folding of hydrogen bonds (interchain, intrachain)
- Alpha helices
- Beta pleated sheets
secondary structure
banned in Paris on 1566
tartar emetic
PROTEIN STRUCTURES OR CONFORMATIONS
- various bonds
- Functional (Native)
- Polypeptide (single subunit)
- Ex. Myoglobin
Tertiary structure
PROTEIN STRUCTURES OR CONFORMATIONS
- More than 1 subunits
- Ex. Hemoglobin (4 subunits)
Quaternary structure
Important component of collagen for strength
hydroxyproline
addition of hydroxyl
Proline will undergo ____ (chemical reaction) to form hydroxyproline
hydroxylation
Hydroxylation need ____ to produce many hydroxyproline
Vitamin C / Ascorbic acid
- can be seen in the parietal cell of the stomach
- Exchange of potassium and proton
- proton will be released by parietal cell which higher of proton
- once proton secreted, it will react with chloride forming ultimately hydrochloric acid
proton pump
↑H+ = ↑HCl =
hyperacidity
blocks proton pump
proton pump inhibitor
- Biological catalysts
- Lower activation energy
enzymes
chemical reaction Without enzyme
slow
chemical reaction With enzyme
faster
enzyme that can convert oligosaccharides (complex carbohydrate) into monosaccharides (simple carbohydrate)
alpha-glucosidase (AG)
↑ AG = ↑ glucose = ↑ blood glucose =
diabetes mellitus
Alpha-glucosidase inhibitors
antidiabetic
* Acarbose
* Voglibose
* Miglitol
a functional macromolecule cell component with specific stereochemical configuration where a ligand interacts usually in a lock-and-key fashion
receptors
RECEPTORS
only allows bindings of specific compound
specific
RECEPTORS
candidates for binding ; it can be natural compounds (neurotransmitters, hormones, autacoids), exogenous (xenobiotics)
ligand
TYPES OF RECEPTORS
- aka Ionotropic Receptor/ Ligand-gated ion channels (LGICs)
- membranous, cell membrane
- onset: milliseconds (instant effect, fastest onset)
- Allow movement of ions
TYPE 1 RECEPTOR
1onotropic, 1nstant
TYPES OF RECEPTORS
Type 1 receptor is also known as
Ionotropic receptor
Ligand-gated ion channels
TYPES OF RECEPTORS | TYPE 1
more cations inside cell
depolarized
excited / active cells
TYPES OF RECEPTORS | TYPE 1
more anions inside cell
hyperpolarized
depressed or relax
TYPES OF RECEPTORS
- Most abundant receptors in the body
- aka 7-transmembrane or heptahelical; Serpentine receptor (snake-like appearance)
- G-protein-coupled receptor; Metabotropic receptor
- cell membrane
- onset: seconds
type 2
TYPES OF RECEPTORS
Type 2 receptor is also called
G-protein coupled receptor
Metabotropic receptor
Serpentine receptor
TYPES OF RECEPTORS
signaling protein and has 3 subunits (alpha, beta, gamma)
G protein
Alpha-1 receptors are
GPCRs
responsible for contraction in muscles
calcium
TYPES OF RECEPTORS
-
Kinase-linked receptor (Tyrosine-kinase linked
receptor)
➢ Transferase of Phosphate - Onset: minutes
- Examples:
➢ Insulin receptor - ↓blood sugar
➢ Growth Factor receptor
❖ platelet-derived GF; epidermal GF
type 3
act as kinase
tyrosine residues
- Lower blood glucose levels
insulin receptor
-
Gene-transcription-linked receptor
➢ RNA - Nucleus: “Nuclear receptor”
- Onset: hours
- Steroidal hormone receptor
- Thyroid hormone receptor
- Vitamin D & Vitamin D derivatives
type 4
receptors for hypertension
alpha 1
The interaction of a drug with a macromolecular target involves a process known as
binding
a specific area of the macromolecule where binding takes place
binding site
Most drugs interact through weaker forms of interaction known as
intermolecular bonds
Drug and target must have
complementary interactions
include electrostatic or ionic bonds, hydrogen bonds, van der Waals interactions, dipole–dipole inter- actions, and hydrophobic interactions.
intermolecular bonds
INTERMOLECULAR BONDS
➢ Opposite charges (electrostatic forces) [+ & -]
➢ Weaker than covalent bond
➢ Distance-dependent
ionic bond
INTERMOLECULAR BONDS
➢ H + electronegative atom (F,O,N)
➢ Weak
➢ Reversible
H-bond
INTERMOLECULAR BONDS
➢ Non-polar (weak)
➢ Reversible
hydrophobic interactions
Van der Waals
London dispersion
INTERMOLECULAR BONDS | H-bond
this compound leads to phototoxicity
Flourine
INTERMOLECULAR BONDS
- not ideal
- strong bond – drugs will not be released -> will lead to toxicity
- drugs with heavy metal
- Strongest = permanent
- Irreversible (↑ toxic)
- Examples:
➢ Phenoxybenzamine – irreversible; non-selective α
blocker
➢ Organophosphates – irreversible anticholinesterase
covalent bond
CLASSIFICATION OF LIGANDS (DRUGS)
activator ; both have affinity and intrinsic activity
agonist
CLASSIFICATION OF LIGANDS (DRUGS)
AGONIST:
IA = 1
full
CLASSIFICATION OF LIGANDS (DRUGS)
AGONIST;
IA more than 0, less than 1
partial
CLASSIFICATION OF LIGANDS (DRUGS)
AGONIST:
IA less than 0
inverse
CLASSIFICATION OF LIGANDS (DRUGS)
have affinity but without intrinsic activity
antagonist
ability of drug to bind to receptors
affinity
ability of drug to activate the receptor
intrinsic activity
