3-HYDROXYPHTHALOYL-BETA-LACTOGLOBULIN .1. OPTIMIZATION OF PRODUCTION AND COMPARISON WITH OTHER COMPOUNDS CONSIDERED FOR CHEMOPROPHYLAXIS OFMUCOSALLY TRANSMITTED HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1
Ar. Neurath et al., 3-HYDROXYPHTHALOYL-BETA-LACTOGLOBULIN .1. OPTIMIZATION OF PRODUCTION AND COMPARISON WITH OTHER COMPOUNDS CONSIDERED FOR CHEMOPROPHYLAXIS OFMUCOSALLY TRANSMITTED HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1, Antiviral chemistry & chemotherapy, 8(2), 1997, pp. 131-139
Modification of the major bovine whey protein, beta-lactoglobulin (bet
a-LG) by 3-hydroxyphthalic anhydride (3HP) leads to the generation of
a potent inhibitor of infection by human immunodeficiency virus (HIV)
types 1 and 2, designated 3HP-beta-LG. 3HP-beta-LG also has antiviral
activity against herpesviruses, albeit at concentrations exceeding tho
se required for inhibition of HIV-1 infection. The topical application
of 3HP-beta-LG to decrease the rate of sexual transmission of HIV and
other sexually transmitted viruses worldwide is being considered. Res
ults presented here: (i) define the conditions for chemical modificati
on of beta-LG by 3HP, resulting in 3HP-beta-LG with optimum anti-HIV-1
activity; (ii) show that beta-LG, prior to chemical modification, or
3HP-beta-LG can be exposed to the elevated temperatures used to pasteu
rize milk without adversely affecting anti-HIV-1 activity; (iii) provi
de evidence that 3HP-beta-LG is a more potent anti-HIV-1 compound than
sulphated polysaccharides, other candidate compounds considered as pr
ophylactic agents to prevent sexual transmission of HIV-1; and (iv) co
nfirm that the primary target for 3HP-beta-LG is CD4, although binding
to the HIV-1 envelope protein gp120 was also observed and contributed
to the antiviral activity of 3HP-beta-LG.