Question

2) Migraine is the 3d most prevalent illness in the word, with about 1 in 8 people suffering occasionally from these intensely painful and incapacitating headaches. More than 4 million people in the US alone have chronic, daily migraines1. Antagonists of the human calcitonin gene-related peptide receptors (CGRPs) are promising candidates for antimigraine drugs. One effective early treatment for migraines was a CGRP antagonist called olcegepant (BIBN4096BS), which was discontinued mainly because it could not be delivered orally It is important to demonstrate that CGRP and olcegepant interact specifically with each other The complexation of CGRP and olcegepant has been shown by crystallography (3N7S), but experimental evidence of this interaction is required. Unlike the published crystal structure, a labeling experiment could show that the binding is specific even in the presence of other proteins, DNA, etc Explain, in a series of high-quality figures, how the label-transfer reagent Sulfo-SAED could be used to fluorescently label CGRP after it binds with olcegepant. You may assume that the primary amine of the Lys in olcegepant is not involved in the binding interactions. Hint: Which molecule is the "bait" and which is the "prey"? Assemble the figures using a combination of PowerPoint, PDB structures, and ChemSketch or other programs. For instance, images from PDB and ChemSketch can be assembled in PowerPoint, grouped together, and then copied to the clipboard or saved as an image file Use "Paste Special. -» Enhanced Metafile (EMF)" to insert the composite image into MS Word (or a similar program). Neatness and readability are important (i.e. for full points) Don't forget to turn off display of the bound olcegepant ligand on 3N7S for your uncomplexed protein structures.

Please draw the structure if you think it needs to draw. Clear progress will be helpful.

Have a nice day!

Answer 1

the label -transfer reagent Sulfo- SAED could be used to fluorescently label CGRP after it binds with olcegepant because Sulfo-SAED has fluorescent spacer arm due to presence of azidomethlycoumarin acetamide (AMCA) group at photoactive end.AMCA is a light sensitive azide on the aromatic ring.

photolyzing with the light in the long uv range will result in non-selective bond formation.