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SUBSTRATES FOR RIBOSOMAL PEPTIDYL TRANSFERASE - SYNTHESIS OF 3'-N-AMINOACYL AND 5'-O-NUCLEOTIDYL ANALOGS OF PUROMYCIN

journal contribution
posted on 2023-02-07, 01:17 authored by RJ HARRIS, Julian MercerJulian Mercer, DC SKINGLE, RH SYMONS
The chemical synthesis, on a 10–30 μmol scale, of two series of puromycin analogues is described: the first is the type 3′-N-aminoacyl-puromycin aminonucleoside (e.g. 3′-N-glycyl-PANS or PANS-Gly) in which the O-methyl-L-tyrosyl residue of puromycin is replaced by various aminoacyl residues, and the second is the type NpPANS-Gly in which the 5′-hydroxyl of PANS-Gly is substituted with phosphate, 3′-AMP, 3′-CMP, 3′-GMP, or 3′-UMP. The 3′-N-aminoacyl-PANS derivatives were synthesized either by coupling N-protected amino acids via their N-hydroxysuccinimide esters to PANS in 70% aqueous pyridine or by direct coupling in ethanol or methanol of N-protected amino acids to PANS using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) as condensing agent After removal of the protecting groups, reaction mixtures were purified by preparative thin-layer chromatography on silicic acid, paper chromatography, and paper electrophoresis to give the 3′-N-aminoacyl-PANS derivatives in yields of 40–80%.The 5′-O-nucleotidyl derivatives of PANS-Gly were synthesized by three methods: (i) by the coupling of fully acetylated 3′-mononucleotides to 3′-N-(Boc-glycyl)-PANS, (ii) by the coupling of N4-acetyl-2′,5′-di-O-tetrahydropyranylcytidine or N2,O2′,O5′-tritetrahydropyranylguanosine to 5′-O-phosphoryl-(Boc-glycyl)-PANS, and (iii) by the coupling of N4-acetyl-2′,5′-di-O-tetrahydropyranyl-3′-CMP or N2,O2′,O5′-tritetrahydropyranyl-3′-GMP to 3′-N-Boc-PANS or 3′-N-trifluoroacetyl-PANS followed by aminoacylation of the CpPANS or GpPANS produced with Boc-glycine and EEDQ. Coupling reactions were carried out using either N,N′-dicyclohexylcarbodiimide or 2,4,6-triisopropylbenzenesulfonyl chloride as condensing agents in anhydrous pyridine. After removal of protecting groups, reaction mixtures were purified by paper chromatography and paper electrophoresis to give the NpPANS-Gly derivatives in 3–30% yield.

History

Journal

CANADIAN JOURNAL OF BIOCHEMISTRY

Volume

50

Pagination

918-&

Location

Canada

ISSN

0008-4018

Language

English

Publication classification

CN.1 Other journal article

Issue

8

Publisher

NATL RESEARCH COUNCIL CANADA

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