Enhanced hydrophobicity at the loop of desmopressin improves its antiproliferative activity

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

San Diego

Simposio; 22nd American Peptide Symposium; 2011

American Peptide Society

  Desmopressin (dDAVP), a synthetic analog of the vasopressin (AVP) hormone, shows in vitro antiproliferative activity when incubated with MCF-7 cells [1]. dDAVP is a safe hemostatic peptide with proved antimetastastic properties in breast cancer models in mice and veterinary clinical trials [2]. Consequently, dDAVP results an interesting lead compound for the development of novel synthetic peptide analogs with enhanced antitumor properties. It is postulated that the antiproliferative activity is mediated by the interaction with the V2 receptor (V2R) and that enhanced hydrophobicity at the cyclic part of the peptide improves this interaction [3]. V2R are expressed in renal collecting ducts, mediating the antidiuretic action, in endothelial cells, mediating most of the non-renal effects, and also in some human tumor cells, such as breast cancer cells [4]. In order to improve this interaction, substitutions at the loop of the peptide were performed, specifically at positions 4 and 5. Antiproliferative activity of dDAVP and two analogs ([V4]dDAVP and [V4Q5]dDAVP) was assayed on human breast cancer cells, expressing V2R (MCF-7).