Antimyristoylation of the gag proteins in the human immunodeficiency virus-infected cells with N-myristoyl glycinal diethylacetal resulted in inhibition of virus production.
The gag proteins of human retroviruses such as human immunodeficiency virus (HIV-1) are specifically myristoylated in their amino termini (1, 2, 3). N-myristoyl glycinal diethylacetal (N-Myr-GOA) and other N-Myr-compounds (N-Myr-Gly-GOA, N-Myr-Gly-Gly-GOA and N-Myr-Gly-Gly-Gly-GOA) were newly synthesized and investigated for activity of antimyristoylation of these gag proteins and for influence on viral replication. Of the N-Myr-compounds tested, N-Myr-GOA most severely inhibited the protein myristoylation; N-Myr-Gly-GOA also inhibited it, but moderately. Furthermore, it was observed that N-Myr-GOA at 20 microM caused noticeable inhibition (about 80%) of the production of mature HIV in the HIV-1-infected MT-4 cells. In this system, N-Myr-GOA substantially inhibited more than 90% of the N-myristoylation of p17 gag protein produced in the HIV-1-infected MT-4 cells. These results suggest that the N-myristoylation of p17 gag protein of HIV-1 may be essential in its structural assembly or maturation.
Tashiro
A
A
Department of Biochemistry, Faculty of Pharmaceutical Science, Kumamoto University, Japan.
Shoji
S
S
Kubota
Y
Y
D000079:Acetaldehyde / Q000494:pharmacology*; D000080:Acetals / Q000494:pharmacology*; D002460:Cell Line; D015683:Gene Products, gag / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism* / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
D000080:Acetals; D015683:Gene Products, gag; D009227:Myristic Acids; D019814:Myristic Acid; C057591:N-myristoyl glycinal diethylacetal; D000079:Acetaldehyde