Drug Binding Interactions Flashcards
What do drugs bind to?
Target receptor/enzymes
transport proteins
metabolizing enzymes
additional sites
Interaction between drug molecule and receptor depends on ?
functional groups on the receptor and drug
types of bonds that the functional groups can form with one another
number and relative strengths of bonds
Covalent bonds
strongest types of bonds
not readily reversible
generally involves a nucleophilic attack and a lone pair of electrons or a negative charge
What is required to reverse covalent bonds?
biosynthesis of a new copy or enzymatic cleavage
Some compounds that form covalent, irreversible bonds may require?
specific handling and guidelines
What are the four most common mechanisms to make covalent bonds?
alkylation
acetylation
phosphorylation
rearrangement
Alkylation
adds an alkyl group
acylation
add acyl groups
Phosphorylation
addition of a nucleophile to make a phosphate
What are the types of non covalent bonds?
ionic
ion-dipole
dipole
van der Waals
Aromatic interactions
chelation and complexation
Most drugs bind and form one or more types of ?
noncovalent bonds
Noncovalent bond strength?
0.5-10 Kcal/mol
Are noncovalent reaction reversible?
yes
As bond distance increases, bond attraction?
decreases
If a functional group blocks binding site, what happens to the affinity of a drug and the receptor?
decrease it
Ionic bonds
over the greatest distance, often initial recognition between the drug and the receptor
between acidic and basic functional groups or ionized acidic and quaternary ammonium functional groups
Dipole interactions
occurs between functional groups with a partial charge separation
Which two elements are more electronegative than C and H?
O and N
Is there a dipole between C and H?
no
Ion-dipole
bond between a full charge and a partial charge
Dipole-dipole
bond between two partial charges
Hydrogen bonds
the most common of dipole-dipole interactions
generally stronger than normal dipole-dipole bonds
hydrogen serves as a bridge between 2 electronegative atoms
What is the ranking of best donor and acceptor using the XHY designation?
OHN>OHO>NHN~NHO
When XHY is collinear, what occurs?
the strongest hydrogen bonds
H bond formation helps with?
dissolution
reinforced ionic bond
hydrogen bonds work with ionic bonds to enhance the overall bond strength
What will an ionized functional group participate in? What will it not participate in?
Will- ionic bonds, ion-dipole bonds
won’t - dipole-dipole or pure H bond
van der Waals Interactions
occur between non polar groups
highly distance specific
weak
no measurable dipoles
mutual polarization results in a dipole-induced dipole interactions
What types of bonds can easily distribute electrons and form a dipole?
C-C and C-H
Water molecules have what ability when they encounter a lipid surface?
to become highly ordered
When two hydrophobic regions bind what happens to entropy?
it increases
Why doesn’t every carbon group contribute to binding energy?
- they may be electron donating
- they may be in a polar region of a receptor and decrease the availability of lipid soluble functional groups
- not every carbon atom meets steric dimensions
- not every carbon atom is in the active site
Charge transfer interactions
between electron rich and electron poor aromatic rings
pi-pi stacking interactions
involves electron clouds of aromatic rings
similar to a van der Waals interaction but also involves polar movements
cation-pi interactions
occur due to the attraction of a positively charged group to the electrons in a pi cloud of an aromatic ring
chelation
when 2 distinct electron donating groups present on the same molecule, bind to a metal ion and form a ring structure
metal complexation
whenever a metal ion interacts with a single atom but does not form a ring
