Blocking of CD4 cell receptors for the human immunodeficiency virus type 1 (HIV-1) by chemically modified bovine milk proteins: potential for AIDS prophylaxis.
The chemical transformation of synthetic combinatorial libraries to increase the diversity of compounds of medicinal interest was reported recently. Chemical modification of natural products represents a complementary approach to accomplish this aim. Modification of lysines by aromatic acid anhydrides, preferentially by 3-hydroxyphthalic and trimellitic anhydrides and trimellitic anhydride chloride, converted commonly available proteins (human and bovine serum albumin and casein) into potent inhibitors of (i) binding between the HIV-1 gp 120 envelope glycoprotein and the CD4 cell receptor, probably owing to their binding to CD4, and (ii) infection by HIV-1. Modified bovine milk proteins are also potent HIV-1 inhibitors and may have potential for anti-HIV-1 prophylaxis.
Neurath
A R
AR
Laboratory of Biochemical Virology, Lindsley F. Kimball Research Institute of the New York Blood Center, New York 10021, USA.
Debnath
A K
AK
Strick
N
N
Li
Y Y
YY
Lin
K
K
Jiang
S
S
D000812:Anhydrides; D000818:Animals; D000911:Antibodies, Monoclonal; D000998:Antiviral Agents / Q000494:pharmacology*; D001120:Arginine; D015704:CD4 Antigens / Q000737:chemistry* / Q000187:drug effects* / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002417:Cattle; D005260:Female; D006678:HIV / Q000502:physiology*; D006801:Humans; D008239:Lysine; D008894:Milk Proteins / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000812:Anhydrides; D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D015704:CD4 Antigens; D008894:Milk Proteins; D012710:Serum Albumin, Bovine; D001120:Arginine; D008239:Lysine