Hello, I was wondering if it is possible to make a protein antagonist that binds to three different receptors, instead of making 3 different antagonists.

For example, I made this diagram that has the isdA, isdB, and isdH receptors, and im wondering if I can make 1 antagonist that fits to all three.


If its possible, do you have any information on how to synthesize these?

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I can only offer generalities here! You can certainly make antibodies (which are proteins) that can bind (and may block function) to all three of these surface receptors (see - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539746/), but you would have to do some reading to establish whether one antibody or vaccine could be/has been produced against all three - e.g., is there enough similarity between the antigenic epitopes of the three receptors?

There may also be antibacterials, not necessarily proteins, already in existence that recognise IsdA/B/H to interfere with heme binding and/or transport-function, although you would not classify many of these drugs (such as porphyrins - see http://www.ncbi.nlm.nih.gov/pubmed/11178343) as true receptor ‘antagonists’ (e.g., they may bind to Isd’s to ‘piggy-back’ into the cell, mimicking the binding properties of the natural ligand, and there exert antimicrobial activity).

As to receptor ‘antagonists’ in general there are protein antagonists that can block the activity of any number of receptors particularly in a closely-related receptor family, if there is sufficient structural similarity in the antagonist binding domains. A pan-specific receptor antagonist may often have differing affinities between receptors.

Designing such an antagonist has traditionally been based on identifying a candidate from a screen of ‘lead’ compounds that might bind to a number of receptors. It is then usually chemically refined to increase its affinity and specificity to one receptor (often to reduce off-target effects). As the 3D structures of more and more receptors are being elucidated a lot of effort is being invested in computer-aided molecular modelling (‘locking and docking’) of receptor ligands. This is mostly the remit of highly specialised labs.

see also - https://en.wikipedia.org/wiki/Antimicrobial_peptides

Last edited by Steve Lolait (16th Apr 2016 09:56:47)