Synthesis, conformation, and bioactivity of novel analogues of the antiviral lipopeptide halovir A.
We synthesized by solution-phase methods three analogues, [L-Leu(6)-OMe], [L-(alphaMe)Leu(3), L-Leu(6)-OMe], and [L-(alphaMe)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-(alphaMe)Leu- and L-(alphaMe)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-(alphaMe)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.
Dalla Bona
Andrea
A
Department of Chemistry, University of Padova, 35131 Padova, Italy.
Formaggio
Fernando
F
Peggion
Cristina
C
Kaptein
Bernard
B
Broxterman
Quirinus B
QB
Galdiero
Stefania
S
Galdiero
Massimiliano
M
Vitiello
Mariateresa
M
Benedetti
Ettore
E
Toniolo
Claudio
C
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D018259:Herpesvirus 1, Human / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014709:Vero Cells
D000998:Antiviral Agents; D010455:Peptides