Synthesis, conformation, and bioactivity of novel analogues of the antiviral lipopeptide halovir A

✍ Scribed by Andrea Dalla Bona; Fernando Formaggio; Cristina Peggion; Bernard Kaptein; Quirinus B. Broxterman; Stefania Galdiero; Massimiliano Galdiero; Mariateresa Vitiello; Ettore Benedetti; Claudio Toniolo

• Book ID: 105360632
• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 197 KB
• Volume: 12
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/psc.808

✦ Synopsis

Abstract

We synthesized by solution‐phase methods three analogues, [L‐Leu^6^‐OMe], [L‐(αMe)Leu^3^, L‐Leu^6^‐OMe], and [L‐(αMe)Val^4^, L‐Leu^6^‐OMe] of halovir A. The [L‐Leu^6^‐OMe] analogue is known to be biologically equipotent to its naturally occurring, antiviral, lipopentapeptide amide parent compound. The preferred conformations of the L‐(αMe)Leu‐ and L‐(αMe)Val‐containing analogues, with a potentially reinforced helicity, were compared with those of [L‐Leu^6^‐OMe] halovir A and the natural peptide itself by use of a combination of FT‐IR absorption and NMR techniques. Measurements of the antiviral activities against herpes simplex virus type‐1 (HSV‐1) of halovir A and its three analogues were also carried out. Interestingly, the [L‐(αMe)Val^4^, L‐Leu^6^‐OMe] analogue exhibits the most significant activity in reducing HSV‐1 infectivity, notably higher than that of halovir A itself. Copyright © 2006 European Peptide Society and John Wiley & Sons, Ltd.