NOVEL ANTIMICROBIAL PEPTIDES DERIVED FROM HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 AND OTHER LENTIVIRUS TRANSMEMBRANE PROTEINS

We have previously described a conserved set of peptides derived from lentiviral envelope transmembrane proteins that are similar to the nat ural antimicrobial peptides cecropins and magainins in overall structu re but bear no sequence homology to them or other members of their cla ss. We describe here an evaluation of the antimicrobial properties of these virally derived peptides, designated lentivirus lytic peptides ( LLPs). The results of this study demonstrate that they are potent and selective antibacterial peptides: the prototype sequence, LLP1, is bac tericidal to both gram-positive and gram-negative organisms at micromo lar concentrations in 10 mM phosphate buffer. Furthermore, LLP1 kills bacteria quite rapidly, causing a 1,000-fold reduction in viable organ isms within 50 s. Peptides corresponding to sequences from three lenti virus envelope proteins were synthesized and characterized. Several of these peptides are selective, killing bacteria at concentrations 50- to 100-fold lower than those required to lyse erythrocytes. Developmen t of antimicrobial agents based on these peptides may lead to improved therapeutics for the management of a variety of infectious diseases.