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Tetrahydropyrimidine derivatives inhibit binding of a Tat‐like, arginine‐containing peptide, to HIV TAR RNA in vitro
Author(s) -
Lapidot Aviva,
Ben-Asher Edna,
Eisenstein Miriam
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00514-a
Subject(s) - tar (computing) , chemistry , peptide , in vitro , rna , arginine , in vivo , biochemistry , binding constant , stereochemistry , delocalized electron , binding site , microbiology and biotechnology , amino acid , biology , organic chemistry , programming language , computer science , gene
The ability of a small molecule, 2‐methyl,4‐carboxy,5‐hydroxy‐3,4,5,6‐tetrahydropyrimidine (THP(A)), which accumulates intracellularly in various streptomyces, to inhibit the interaction of Tat peptide (R52) with TAR RNA is presented. Using gel‐shift assay, we found that the inhibition constant K i of THP(A) is 50–100 nM, which is in the range of the binding constants of Tat peptide and protein. THP(A) is ∼ 10 6 times more tightly bound than the free l ‐arginine. The high binding affinity may be attributed to the special delocalized positive charge on the NCN group and the hydroxyl group at the 5 position of this molecule. A model for THP(A)‐TAR interaction, analogous to the arginine guanidinum group‐TAR interaction, is presented. The relatively high uptake of THP(A) by mammalian cells warrants in vivo Tat/TAR inhibition studies.