$($a$)$ Answer All Parts

$[50$ marks$]$

$($i$)$ In your company a new protein was identified that appears to be abundant

in individuals prone to a certain type of cancer and you are trying to develop

a molecule that will inhibit this protein's activity $-$ a potential drug candidate.

The protein structure and function has been elucidated $($including active site$)$

and the protein can be produced using cloning methods, $($that is the protein

can be made$/$grown and isolated in pure form$).$ As research director, you

have been asked to develop a work program$/$approach to find a potential

drug candidate for this protein. Your company has available an unlimited

budget and any equipment$/$personnel that may be needed for your proposed

work program $($robotic synthesis, HTS technology, $400-800MHz$ NMR

equipment, high resolution mass spectrometry, $x-$ray crystallography etc.$).$

Give a step by step outline of your proposed work plan and explain your

rational. Feel free to include diagrams in your answer. $[35$ marks$]$

$($ii$)$ The following compound has very poor bioavailability. Why does this

compound have poor bioavailability and how would you improve the

bioavailability using bioisostere replacement. Explain why your new

compound would have enhanced bioavailability. $[15$ marks$]$

$($b$)$ Answer All Parts

$[50$ marks$]$

$($i$)$ Metallodrugs can be deactivated by peptides such as glutathione and

metallothionine. Describe in detail synthetic strategies that can be used to

enhance the biological stability of platinum compounds. Include relevant

structures and schemes in your answer. $[25$ marks$]$

$($ii$)$ Describe in detail the synthetic method used to prepare the anticancer drug

cisplatin, cis$-Pt(N{H}_3{)}_{2}C{l}_2.$ Compare this method to that used to develop the

less active isomer, trans$-[\{$:$Pt(N{H}_3{)}_{2}C{l}_2].$ Describe one suitable spectroscopic

and one suitable molecular $($or biophysical$)$ assay you could use to

distinguish both cis$-$ and trans$-$ isomers. Include relevant structures and

schemes in your answer. $[25$ marks$]$