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Guerrini R et al. – The primary sequence of NPS is highly conserved among vertebrates especially at the N–terminus. Ala– and D–scan studies demonstrated that this part of the molecule is crucial for biological activity. Focused structure–activity studies performed on Phe2, Arg3, and Asn4 confirmed this indication and revealed the chemical requirements of these positions for NPSR binding and activation. The use in future studies of NPSR antagonists will be of paramount importance for understanding which biological functions are controlled by the NPS/NPSR system and for defining the therapeutic potential of selective NPSR ligands.

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