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CHM 708: MEDICINAL CHEMISTRY
Proteins
a-Amino-acids: Building blocks of
proteins
Proteins are made up of 20 major aminoacids with different side chains
Peptide bonds
Primary Structure
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A protein consists of a long chain (50 or
more) or polymer of a-amino-acids, linked
together by peptide (amide) bonds.
Short chains are called peptides.
The free NH3+ end is called the N-terminus,
and the free CO2- end the C terminus.
The primary structure of a protein is the
sequence of amino-acids in the chain.
The sequence of -N–C–C- segments in the
chain is called the backbone.
Secondary Structure
This refers to the local spatial arrangement
of the backbone atoms of segments of the
protein chain.
 Three main types:
◦ a-Helix
◦ b-Sheet
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◦ Irregular coils.
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All are stabilised by H-bonding between
backbone NH and C=O groups.
a-Helix
b-Strand (anti-parallel)
b-Strand (parallel)
b-Sheet
Tertiary structure
This is the overall arrangement of all the
atoms in the protein, i.e., its overall shape.
 Every protein has a natural tertiary structure
– most stable shape. It is active only in
that shape.
 Tertiary structure is determined by primary
structure.
 Tertiary structure is stabilised by H-bonds,
ionic bonds, polar interactions, hydrophobic
interactions, dispersion (Van der Waals)
forces, and certain types of covalent bonds.
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Tertiary structures
Fatty-acid binding protein
Myoglobin
Multi-subunit Proteins
Some complex proteins consist of two or
more amino-acid chains.
 Each chain is called a subunit and has its
own tertiary structure.
 The arrangement of subunits in the overall
protein is called the quaternary structure.
 Quaternary structure is stabilised by the
same forces as tertiary structure. So is the
binding of small molecules to specific
sites on the surface of the protein.
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Quaternary structure
Yellow: a subunits
Red: b subunits
Haemoglobin
Functions of proteins
Structural proteins (skin, hair, nails, etc.)
 Muscle proteins (able to contract, use
energy to do work).
 Transport proteins.
 Cell membrane proteins.
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◦ Membrane channels and pores
◦ Molecular recognition and signalling.
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Enzymes: catalysts of biological reactions.
◦ Membrane-bound
◦ Intra-cellular
◦ Extra-cellular.
Protein-ligand binding
Most proteins function by, or as a result of,
reversibly binding a small molecule (ligand).
 Each ligand has a specific binding site
(active site), into which it fits.
 The binding of a particular ligand to a
protein can be modulated by other ligands
binding to the same protein.
 Drug molecules binding to the protein at
the active site or other sites can interfere
with its normal functioning.
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