Abstract:
:The receptor for the neuropeptide relaxin 3, relaxin family peptide 3 (RXFP3) receptor, is an attractive pharmacological target for the control of eating, addictive, and psychiatric behaviors. Several structure-activity relationship studies on both human relaxin 3 (containing 3 disulfide bonds) and its analogue A2 (two disulfide bonds) suggest that the C-terminal carboxylic acid of the tryptophan residue in the B-chain is important for RXFP3 activity. In this study, we have added amide, alcohol, carbamate, and ester functionalities to the C-terminus of A2 and compared their structures and functions. As expected, the C-terminal amide form of A2 showed lower binding affinity for RXFP3 while ester and alcohol substitutions also demonstrated lower affinity. However, while these analogues showed slightly lower binding affinity, there was no significant difference in activation of RXFP3 compared to A2 bearing a C-terminal carboxylic acid, suggesting the binding pocket is able to accommodate additional atoms.
journal_name
ACS Med Chem Lettjournal_title
ACS medicinal chemistry lettersauthors
Praveen P,Tailhades J,Rosengren KJ,Liu M,Wade JD,Bathgate RAD,Hossain MAdoi
10.1021/acsmedchemlett.0c00456subject
Has Abstractpub_date
2020-10-22 00:00:00pages
2336-2340issue
11issn
1948-5875journal_volume
11pub_type
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