Module #2 - Biotargets of Drugs Flashcards
what are the four main types of biological molecules
proteins
nucleic acids
polysaccharides
lipids (fats and steroids)
describe simple/overall structure of proteins
linear chain of amino acids connected by amide (peptide) bonds
describe structure of nucleic acids
linear chain of nucleotides connected by phosphate esters
describe structure of polysaccharides
linear chain of sugars, some branched
connected by acetals
describe structure of lipids
linear chains of acetate or propionate
connected by reduced aldol
what is responsible for assembling and disassembling proteins
ribosomes assemble
proteasome disassemble
why are biological molecules modular?
fit together like building blocks
provide body with simple way to make lots of different molecules
why is modular construction important?
allows for complex structures to be assembled using simple molecule components
allows for complex structures to be disassembled, and to regenerate parts to re-use
make living systems possible
only one enzyme system required for each biomolecule type and function
how are proteins assembled
amino acids are linked together by ribosomes using amide (peptide bonds)
how are proteins disassembled
proteasome break apart the chains of amino acids (and the amide bonds between then)
protein is essentially broken down into individual amino acids
what is the most common drug target in the body?
proteins
how do drugs produce effects in the body?
bind to targets/receptors of biomolecules
results in biological change (ie. shape change)
results in biological response (
importance of 3D effect of biomolecules
allows biomolecules to bind and be recognized
why do drugs follow like-dissolves-like rule
drug will interact with biological molecules with similar chemical properties
what is the general structure of an animo acid?
amine group (NH2)
acid group (COOH)
side chain (r)
all have same stereochemistry/backbones, but different side chains
what are the five major classes of amino acids
nonpolar
acidic
basic
polar
special
what is special about cysteine amino acid?
has R configuration at alpha carbon
sulfur has higher atomic number than oxygen, which reverses priority
describe the primary structure of proteins (2)
involves a sequence of amino acids linked together by peptide (amide) bonds) to form a polypeptide chain
listed in order from N-terminus to C-terminus
describe connections of N and C termini in amino acid linkages (2)
N-terminus has an amine group, and C-terminus has a carboxylate group
N-terminus connects to the C-terminus of another amino acid, forming amide bonds
describe secondary structures of proteins (3)
areas of regular, local order in the protein backbone chain
tend to hold one of the four main types of structures (due to rotating restrictions)
chemical interactions between side chains can influence the shape of secondary structure
originate from conformations available due to amide bonds, and stereogenic enters which restrict rotations
what are the four types of secondary structures
a-helix
b-sheet
loop
turn
what 3 factors lead to the formation of a secondary structure
conformational restrictions in amide bonds
conformational restrictions between amide and alpha carbon
interactions between amide bonds
what two possible shapes can an amide form?
sigma cis (s-cis) or sigma trans (s-trans) conformations
describe the s-trans conformation of amides
2 large groups are far away and don’t interact
preferred/more stable conformation
describe the s-cis conformation of amide
2 large groups eclipse and therefore interact
not preferred/less stable
describe side chain interactions that occur in secondary structures of proteins + their result (4)
negative charges attract positive charges
H bonding occurs between side chains and backbones of proteins
non-polar side chains interact with other non-polar chains
result = localized structure
what is a localized structure in terms of the secondary structure of proteins
the sum of all the effects of side chain interactions adding together to form a secondary structure formation
describe the alpha helix secondary structure of proteins (3)
corkscrew/spiral shape
forms H bonds between amide groups about 4 amino acids apart
represented by ribbon diagrams that follow plane of amide groups in backbone, and includes arrow pointing from N to C terminus
describe the beta structure of secondary proteins (overall)
can take shape of beta strand, beta sheet, or beta barrel
describe the structure of a beta strand (4)
a linear strand of amino acids
zig-zag formation (because amides prefer s-trans formation)
backbone organizes itself so everything is on same plane (so coplanar/flat in nature)
side chains stick out on either side
describe the structure of a beta sheet (4)
formed by several beta strands associating together
can be parallel or antiparallel
held together by hydrogen bonds
flat structures
describe the structure of a beta-barrel
beta sheets curling around themselves to form a cylinder formation
describe structure of a loop (2)
area with no defined secondary structure
thin tube structures
describe structure of turns (3)
areas that change almost 180 degrees with length of 3-4 amino acids
done because of H bonding between nearby amide groups
peptide essentially kinds over onto itself and changes direction
describe tertiary structure of a protein (5)
overall 3D shape of protein
combination of secondary structures added together
result of interactions between non-adjacent regions
mostly non-bonding interactions
disulphide bonds primarily control structure (between 2 cysteine side chains)
what four attractractiv forces are involved in tertiary structures?
disulphide bonding
ionic bonding
hydrogen bonding
van der waal interactions
what is disulphide bonding
most common/strongest covalent bond
involves formation of disulphide bond (typically between 2 cysteine side chains)
what is ionic bonding
also known as salt bridge
involves complete positive and complete negative charges being attracted to each other
what is hydrogen bonding?
involves hydrogen being attracted to a pair of electrons on an atom nearby
what are van der waal interactions
involve greasy side chains interacting with greasy side chains (non-polar non polar interactions)
weak, but not important
what are van der waal interactions
non-polar non-polar interactions (greasy side chains interacting with greasy side chains)
weakest, but most important interaction
why are van der waal interactions important for tertiary structures (4)
allow for side chains on inside of protein to be non-polar, creating an inner non-polar environment
side chains on outside are polar, creating polar environment
non bonding interactions (H bonding and dipole) are weaker on the outside because polar + polar = weakened bonds. nonbonding interactions are stronger on inside because polar + non polar = stronger bonds.
strong inner bonds are what hold the protein together
what are quaternary structures
occurs when two or more tertiary structures of proteins come together to generate larger protein
what type of interactions occur in quaternary structures? why so strong? (4)
protein protein interactions
strong because:
-lots of surface area
-lots of chemical interactions
-exclusion of water from space between so proteins stick tightly together
is most of a protein active or scaffold?
most of protein is just scaffold, only a small part is active
what are the four types of protein targets for drugs?
enzymes
receptors
ion channels
structural proteins
what does a drug do if an enzyme is its target in general?
stops enzyme from working (inhibitors)
what does a drug do if it has receptor for target?
activates (agonist) or deactivates (antagonist)
what does a drug do if it has ion channel for target
opens or closes the channel
what does drug do if it has structural protein for target?
interferes with assembly/disassembly of protein structures
how do enzymes catalyze reactions?
creates a custom environment for transition state of reaction
bind to transition states and lower transition state energy/activation energy accelerating the reaction
describe general process of enzyme catalyzed reactions? (3)
enzyme binds to substrate resulting in some sort of shape change and forming enzyme-substrate complex
reaction occurs forming the enzyme-product complex
product is formed and separates from enzyme
what are the two main theories of enzymatic conformational change? which is correct?
lock and key - enzyme is perfect shape to fit into substrate
induced fit - enzyme/substrate binding changes shape
both correct, but induced fit more realistic
what are Michaelis Menten kinetics?
used to describe efficiency of enzyme
shows kinetics behind enzyme catalyzed reactions
what does a Michaelis Menten plot do?
tracks how an enzyme produces product over time
what are the 4 main types of enzyme inhibition?
competitive inhibition
non-competitive inhibition
un-competitive inhibition
irreversible inhibition
describe competitive inhibition (30
drug competes with substrate molecule for the active site
binds to active site and changes its shape
prevents substrate from binding, therefore product cannot be produced
describe kinetics of competitive inhibition (3)
alters Km and Kcat, but Vmax stays same
Y-intercept stays same
Slope changes
what type of inhibitor is disulfiram? what does it do?
drug for alcoholics
inhibits/blocks acetaldehyde dehydrogenase (chemical that stops body from getting sick due to hangover)
essentially produces wicked hangover to prevent alcoholics from drinking
describe non-competitive inhibition (3)
inhibitor binds to enzyme in spot other than the active site
causes a conformational change to occur which prevents the substrate from being able to properly bind to active site
prevents formation of the enzyme substrate complex
describe kinetics of non-competitive inhibition
changes both slope and y-intercept
alters Kcat and Vmax, but does not change Km
describe uncompetitive inhibition (3)
very rare
inhibitor binds to enzyme-substrate complex instead of enzyme itself (so attaches after substrate has already binded to enzyme)
destroys the catalytic ability of it ES complex (catalysis cannot occur)
describe kinetics of uncompetitive inhibition
alters Kcat Km and Vmax
describe irreversible inhibitors
covalent (suicide) inhibitors
bond covalently to enzyme (usually in active site) and alter conformation/disable functional groups
what is a receptor
a molecule that moves information from one side of membrane to other
specialized proteins in cell membrane
how do receptors transfer information across membrane (4)
messenger approches receptor
shape of receptor changes upon interaction
receptor on other side of membrane becomes activates/changes shape allowing info to be carried
once information has been transmitted, receptor spits out messenger and process starts again
what two ways does information transfer in receptors take place?
binding of messenger changing conformation of receptor allowing another molecule to bind or be released
binding of messenger changing conformation of receptor creating an enzyme active site on receptor
how do ion channels work
acts like a valve
when messenger binds, valve opens allowing ions to flow from one side of membrane to other
what are the 5 main classes of drugs
agonists
antagonists
allosteric antagonists
partial agonists
inverse agonists
what are agonists (3)
activates the receptor in a normal way (essentially acts as messenger)
usually binds in same place as messenger, and induces shape change very similar to normal messenger
biological response increases with increased concentration
what is an allosteric modulator? what drug class does it correspond with? (4)
type of agonist
binds to receptor, but not in same place as normal messenger
alters shape/sensitivity of receptor towards normal messenger which alters the way the two interact going forward
work with ion channels
what are antagonists (4)
binding induces abnormal shape change that results in no signal transmission
changes shape of receptor into shape that is not accessible by regular messenger molecule so that is cannot bind and info cannot be transmitted
may bind at same site as messenger or different
essentially prevent transmission of information
what are allosteric antagonists (3)
binds to active site or somewhere near
does not bind at same place as messenger
disrupts shape of receptor so that messenger cannot bind and therefore information cannot be transmitted
what are partial agonists
similar to agonists but not as strong
binds to receptor and produces non-ideal conformational change.
