09-06-2021-0120 - pyrazole sulfonamide HIV 1 HIV AIDS myristoylation Petersens leishmania (bf1900-40) protozoa (bf1950) neoformans fungus *fungi* (bf1800-1980) **bacteria virus** (bf 1900/1910/1990) lipid raft plasma (1930,1940,1950,1980); A pyrazole sulfonamide inhibitor has been identified that selectively binds T. brucei, competing for the peptide binding site, thus inhibiting enzymatic activity and eliminating the parasite from the bloodstream of mice with African sleeping sickness.[8] azide azo comp dyes for assessment - cytopathology in vitro etc.

Impact on human health[edit]

Cancer[edit]

c-Src is a gene that codes for proto-oncogene tyrosine-protein kinase Src, a protein important for normal mitotic cycling. It is phosphorylated and dephosphorylated to turn signaling on and off. Proto-oncogene tyrosine-protein kinase Src must be localized to the plasma membrane in order to phosphorylate other downstream targets; myristoylation is responsible for this membrane targeting event. Increased myristoylation of c-Src can lead to enhanced cell proliferation and be responsible for transforming normal cells into cancer cells.^[5][13][17] Activation of c-Src can lead to the so-called hallmarks of cancer: upregulation of angiogenesis, proliferation, and invasion.^[18]

Viral infectivity[edit]

HIV-1 utilizes myristoylation on the Matrix protein to target the viral proteins and viral genome to the membrane for budding and viral maturation.

HIV-1 is a retrovirus that relies on myristoylation of one of its structural proteins in order to successfully package its genome, assemble and mature into a new infectious particle. Viral matrix protein, the N-terminal most domain of the gag polyprotein is myristoylated.^[19] This myristoylation modification targets gag to the membrane of the host cell. Utilizing the myristoyl-electrostatic switch,^[12] including a basic patch on the matrix protein, gag can assemble at lipid rafts at the plasma membrane for viral assembly, budding and further maturation.^[17] In order to prevent viral infectivity, myristoylation of the matrix protein could become a good drug target.

Prokaryotic and eukaryotic infections[edit]

Certain NMTs are therapeutic targets for development of drugs against bacterial infections. Myristoylation has been shown to be necessary for the survival of a number of disease-causing fungi, among them C. albicans and C. neoformans. In addition to prokaryotic bacteria, the NMTs of numerous disease-causing eukaryotic organisms have been identified as drug targets as well. Proper NMT functioning in the protozoa Leishmania major and Leishmania donovani (leishmaniasis), Trypanosoma brucei (African sleeping sickness), and P. falciparum (malaria) is necessary for survival of the parasites. Inhibitors of these organisms are under current investigation. A pyrazole sulfonamide inhibitor has been identified that selectively binds T. brucei, competing for the peptide binding site, thus inhibiting enzymatic activity and eliminating the parasite from the bloodstream of mice with African sleeping sickness.^[8]

 https://en.wikipedia.org/wiki/Myristoylation

above. Suicide Commando - H.I.V. +

09-06-2021-0120 - pyrazole sulfonamide HIV 1 HIV AIDS myristoylation Petersens leishmania (bf1900-40) protozoa (bf1950) neoformans fungus *fungi* (bf1800-1980) **bacteria virus** (bf 1900/1910/1990) lipid raft plasma (1930,1940,1950,1980);  A pyrazole sulfonamide inhibitor has been identified that selectively binds T. brucei, competing for the peptide binding site, thus inhibiting enzymatic activity and eliminating the parasite from the bloodstream of mice with African sleeping sickness.[8] azide azo comp dyes for assessment - cytopathology in vitro etc.