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: Ae-hLEP(23-47)-NH2 (I), Ac-hLEP(48-71)-NH2 (II), Ac-hLEP(72-88)-NH2 (III), Ac-hLEP(92-115)-NH2 (IV), Ac-[Ser(117)]-hLEP(116-140)-NH2 (V), Ac-hLEP(141-164)-NH2 (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)]-OB3 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. Copyright (C) 2007 European Peptide Society and John Wiley & Sons, Ltd.