Improved Antiproliferative Activity of Desmopressin Analogs Assessed by Ala Scanning

PASTRIAN MB; GUZMAN F; RIPOLL GV; GARONA J; PIFANO M; CASCONE O; CICCIA GN; ALBERICIO F; GOMEZ DE; ALONSO DF; IANNUCCI N

Simposio; 32nd European Peptide Symposium; 2012

Desmopressin (dDAVP), a synthetic analog of the vasopressin (AVP) hormone, has been extensively used in the treatment of water balance related diseases and some haemostatic disorders. This analog has been modified in order to enhance its specificity and half life1. The biological activity of dDAVP is mediated through its interaction with the V2 receptor (V2R) of renal collecting ducts and endothelium cells. Many authors have reported the presence of V2R in some tumor cells2. Our previous work described the advantages of dDAVP application at the perioperative window during mammary tumor surgery3. We have also reported that 2 substitutions at positions 4 and 5 of dDAVP enhance the antiproliferative activity of the resultant analog, assayed in MCF7 cells4. With the aim of identify other key positions involved in the antiproliferative activity of dDAVP, the Ala scanning analysis of the peptide was carried out. Positions 1 and 6, involved in disulphide bridge formation, were not Ala- substituted in order to maintain the cyclic feature of the peptide. Our findings may result in promising antiproliferative molecules destined to oncologic therapy.