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Hydrolytical Cleavage of TAR‐RNA, the trans ‐Activation Responsive Region of HIV‐1, by a Bis(guanidinium) Catalyst Attached to Arginine
Author(s) -
Kurz Kristina,
Göbel Michael W.
Publication year - 1996
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19960790719
Subject(s) - chemistry , moiety , cleave , stereochemistry , catalysis , arginine , rna , cleavage (geology) , nuclease , ribonuclease , combinatorial chemistry , biochemistry , enzyme , amino acid , geotechnical engineering , fracture (geology) , engineering , gene
Guanidinium compounds imitating the bis(arginine) structural motif of staphylococcal nuclease ( e.g. 3 ) are known to be powerful catalysts for phosphoryl transfer reactions in dipolar aprotic solvents. Compound 3 also accelerates the hydrolysis of RNA (H 2 O, pH 7). However, due to diminished substrate affinity in H 2 O, the rate effects are less pronounced in aqueous than in aprotic solution. To test if a synthetic ribonuclease may be derived from the bis(guanidinium) moiety of 3 by the addition of RNA‐binding substructures, the TAR sequence of HIV‐1 was chosen as a target. The arginine residue of compound 4 serves as an extremely simplified mimic of tat, a protein responsible for boosting the viral transcription by complex formation with TAR. Here, we present the synthesis of 4 and its ability to bind and to cleave efficiently the truncated TAR sequence 1 . In addition, the synthesis of an acridine arginine conjugate, 19 , is reported in preliminary form. Compound 19 associates with 1 and completely blocks the cleavage induced by 4 .