Knowing the quaternary structure of proteins, specifically their surface
properties, provides novel opportunities for enhancing the development of
targeted drug therapies.
(a) Referring to Figure \(14-16\) and the accompanying discussion, predict the
class(es) of amino acids likely to reside on the surface of a protein within a
cell.
(b) Assuming that Glu, Arg, and Asp exist in a functional site of a receptor
molecule on the surface of a cell, provide an amino acid sequence that is
likely to be effective in blocking that site.
(c) The androgen receptor associated with prostate cancer has recently been
targeted using synthetic molecules known generally as peptidomimetics, many of
which incorporate D-amino acid stereoisomers rather than the more naturally
occurring L-amino acid stereoisomers. Why might \(\mathrm{D}\) -amino acid
stereoisomers be especially useful for inhibiting a functional site of the
androgen receptor, or any deleterious functional site for that matter?
(d) Rational drug design is a relatively recent approach to the design of
targeted therapeutic agents. Predict how knowledge of protein structure,
especially surface properties, might be used in rational drug design as
compared with the more classical "trial-and-error" approach.