Hydrolytical Cleavage of TAR-RNA, the <i>trans</i>-Activation Responsive Region of HIV-1, by a Bis(guanidinium) Catalyst Attached to Arginine

Article Article scientifique Article Hydrolytical Cleavage of TAR-RNA, the <i>trans</i>-Activation Responsive Region of HIV-1, by a Bis(guanidinium) Catalyst Attached to Arginine eng 1996 author Kurz Kristina 101071 author Gobel Michael Wilhelm 101413 1967-1979 10.1002/hlca.19960790719 0018-019X http://doi.wiley.com/10.1002/hlca.19960790719 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 (H₂O, pH 7). However, due to diminished substrate affinity in H₂O, 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. Dewey 540 36 Département de chimie organique 141 false Helvetica Chimica Acta 79 7 1b6101bc-6be6-4947-837a-0cb669863bca Article (Published version) Restricted Kurz_et_al-2013-Helvetica_Chimica_Acta.pdf 890427 application/pdf restrictedAccess Faculté des sciences / Section de chimie et biochimie / Département de chimie organique

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Hydrolytical Cleavage of TAR-RNA, the trans-Activation Responsive Region of HIV-1, by a Bis(guanidinium) Catalyst Attached to Arginine	Helvetica Chimica Acta			1996	248	0

Archive ouverte UNIGE

Kurz, Kristina