Antiproliferative effect of 1-deamino-8-D-arginine vasopressin analogs on human breast cancer cells: impact of substitutions at the conformational peptide loop

IANNUCCI, NANCY BEATRIZ; RIPOLL, GISELLA V.; GARONA, JUAN; CASCONE, OSVALDO; CICCIA, GRACIELA; GÓMEZ, DANIEL E.; ALONSO, DANIEL F.

Future Medicinal Chemistry

Future Medicine Group

Año: 2011 p. 1987 - 1993

1756-8919

  Desmopressin (dDAVP) is a vasopressin (AVP) analogue with antitumoral activity in preclinical model and canine protocols. This cyclic nonapeptide was punctually substituted at positions 4 and 5 in order to improve its biological activity and half life. These positions belong to the loop between the disulphide bridge of the molecule. In order to assess the role of this loop in the interaction of dDAVP and its analogues with the V2 receptor in endothelial and some tumor cells. dDAVP, three analogues (AQ, VQ and vQ) and their respective loop tetrapeptides (fragment 2-5) were analyzed comparatively by means of their antiproliferative activity on mammary carcinoma cells MCF7 expressing V2 receptor. The incubation with VQ (100-1500 nM) during 72 h significantly reduced cell proliferation, showing a better performance than dDAVP, AQ and vQ. Interestingly, cell proliferation profiles displayed by the leader compound and respective tetrapeptides were similar at low concentrations, highlighting the role of fragment 2-5 in the V2 receptor interaction.