In vitro evaluation of leptin fragments activity on the ob receptor

In an attempt to identify regions in the leptin molecule responsible for its bioactivity, we tested six related-leptin peptide fragments denoted: Ac-hLEP(23-47)-NH(2) (I), Ac-hLEP(48-71)-NH(2) (II), Ac-hLEP(72-88)-NH(2) (III), Ac-hLEP(92-115)-NH(2) (IV), Ac-[Ser(117)]-hLEP(116-140)-NH(2) (V), Ac-hLEP(141-164)-NH(2) (VI) and their correspondent disulfide bridged dimer forms. The activity of the fragments was evaluated in comparision to leptin, by their ability to interact with leptin receptor using a cytosensor microphysiometer. Our results indicated that the fragments IV and V and [D-Leu(4)]-OB(3) and its human sequence analog were recognized by leptin receptor present in HP-75 cells, in agreement with the results obtained by other workers, validating that this region of the molecule contain the functional epitope of the leptin molecule.