Subject: charge re-inforced Hbond in bioamine GPCRs

From: Renate Griffith <[email-masked]>
Date: Mon, 24 Jan 2000 12:12:55 +1000

Dear all!
Can anybody point me to experimental evidence for the charge re-inforced Hbond
between the protonated amine function of the ligand and the conserved aspartate
of TM3 and its strength? I am aware that if you mutate the aspartate to - say -
an alanine, the binding affinity of ligands goes down (even in this case there
are some controversies in the alpha adrenergic field as to how much it goes down
for antagonists versus agonists)). I don't seem to be able to find the opposite:
what happens if you make an uncharged analogue of - say - adrenaline, with a CH2
group instead of the nitrogen, what is its binding affinity? Or what happens, if
you make an analogue with a quarternary nitrogen (replace the H with CH3), which
still is charged, but does not have a proton attached? Has anybody got any
references and/or binding data (any bioamine GPCR is of interest)? I am
currently chasing up an oldish potential reference from the Melchiorre group in
"Farmaco" about the quarternary nitrogen case. Anybody know about that or has
the paper handy?

Thanks for your help.

Regards
Renate

-- 
Dr. Renate Griffith			Phone: +61 (0)2 4221 3516
Research Fellow				Fax:   +61 (0)2 4221 4287
Department of Chemistry  		Email: [email-masked]
University of Wollongong
Northfields Ave
Wollongong, NSW 2522
Australia