New Alloferon Analogues: Synthesis and Antiviral Properties

We have extended our study on structure/activity relationship studies of insect peptide alloferon (H‐His‐Gly‐Val‐Ser‐Gly‐His‐Gly‐Gln‐His‐Gly‐Val‐His‐Gly‐OH) by evaluating the antiviral effects of new alloferon analogues. We synthesized 18 alloferon analogues: 12 peptides with sequences shortened from N‐ or C‐ terminus and 6  N ‐terminally modified analogues H‐X 1 ‐Gly‐Val‐Ser‐Gly‐His‐Gly‐Gln‐His‐Gly‐Val‐His‐Gly‐OH, where X 1  =   Phe ( 13 ), Tyr ( 14 ), Trp ( 15 ), Phg ( 16 ), Phe(p‐Cl) ( 17 ), and Phe(p‐OMe) ( 18 ). We found that most of the evaluated peptides inhibit the replication of Human Herpesviruses or Coxsackievirus B2 in Vero, HEp‐2 and LLC‐MK 2 cells. Our results indicate that the compound [3‐13]‐alloferon ( 1 ) exhibits the strongest antiviral activity (IC 50  =   38 μ m ) among the analyzed compound. Moreover, no cytotoxic activity against the investigated cell lines was observed for all studied peptides at concentration 165 μ m or higher.