To understand the comparative effect on the anorectic property of the replacement of two Tyr residues at positions 58 and 62 in CART(55-102) by two Tyr(Me) or Phe(NO2) residues, [Tyr(Me)58,62]CART55-102 and [Phe(NO2)58,62]CART55-102 were synthesized. In vivo inhibitory activity on the food intake induced by NPY was compared with that of the parent peptide. [Phe(NO2)58,62]CART55-62 exhibited 2-fold higher anorectic activity on the food intake induced by NPY as compared with the parent peptide. [Tyr(Me)58,62]CART55-102 exhibited less potent anorectic activity than the parent peptide. These results indicate that aromaticity of two Tyr residues in CART55-102 is important for anorectic activity on the food intake induced by NPY and an electrophilic group on aromatic rings such as -NO2 enhanced anorectic activity more than that of the parent peptide. On the contrary, an electron-donating group on aromatic rings (Tyr58,62) such as CH3O- influenced to reduce anorectic activity as compared with the parent p eptide.
Keywords: CART (HUMAN,55-102), ANORECTIC EFFECT, NEUROPEPTIDE Y, inhibitory activity, Solid-phase peptide synthesis
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