Question

4. Briefly (one or two sentences) explain why polyamides (shown below) can inhibit gene transcription. (2 points) Recognition of All 4 Base Pairs go w

Answer 1

Hi there, this is an example for synthetic pyrrole-imidazole polyamides such as DNA‐binding molecules (mimics to natural products netropsin and distamycin). We can designate N-methylpyrrole as Py and N-methylimidazole as Im hydroxypyrrole as Hp amino acids, which will bind their target sequences with exceptionally high affinities. The mechanism of binding involves side-by-side pairing of Py and Im amino acids ( minor groove of DNA ).

Circles with dots represent the lone pairs of N of purines and O of pyrimidines. The polyamide amino acid pairs, the polyamide hairpins could be made by connecting two hairpins turn‐to‐tail (three units of flexible -CH2- groups). This is the reason for inhibition of gene transcription by polyamides.

Py/Im recognize the C–G

Py/Hp recognize the A–T

Py/Py recognize the A–T & T-A

Hp/Py and recognize the T–A

Im/Py recognize the G–C respectively.

C-G C-G C-G Hairpin polyamide T-A G-C N-H Minor groove A-T G20 A-T C-G C-G T- A-T Ao—ANS C-G C-G C-C 5' 3H-

Hope this helped you!

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