E. Kuyl-Yeheskiely

A convenient and general approach to the synthesis of properly protected d-nucleoside-3′-hydrogenphosphonates via phosphite intermediates

Abstract Evidence will be presented to show that the monofunctional phosphitylating reagents bis(N,N-di-ethylamino)chlorophosphine and salicylchlorophosphine are very effective for the preparation of 5′-0,N-protected d-nucleoside-3′-hydrogenphosphonates.

The Telomeric GGGTTA Repeats of Trypanosoma Brucei Contain the Hypermodified Base J in Both Strands

We have previously shown that nuclear DNA of bloodstream from Trypanosoma brucei contains a novel base beta-glucosyl-hydroxymethyluracil, called J. Base J is enriched in minichromosome fractions but not in the minichromosome internal repeats, suggesting the association of J with telomeric DNA. To test whether J is present in the long telomeric (GGGTTA)n repeat arrays, which are 2-26 kb in T.brucei, we have purified these arrays both by hybrid selection and by isolating 2-26 kb fragments from DNA digested with multiple restriction enzymes. We find that in purified telomeric repeats approximately 13% of T is replaced by J, compared to 0.8% in total DNA, and we estimate that approximately 50% of the total J is in these repeats. Highly purified complementary strands of the repeats were obtained by alkaline CsCl equilibrium centrifugation. In the (TAACCC)n strand 14% of T was replaced by J. In the (GGGTTA)n strand approximately 36% of the second T was replaced by J; the first T was not detectably replaced. Modified bases have not been found in telomeric repeats before. How the bulky base J affects telomere function and structure in bloodstream form trypanosomes remains to be determined.

One-step synthesis of optically active benzyl N-trityl-L-aziridine-2-carboxylic esters

Abstract Benzyl N-trityl-L-serine or threonine esters give upon treatment with sulphuryl chloride the corresponding benzyl (2s)-1-trityl-2-aziridine carboxylate or (2S, 3S)-1-trityl-3-methyl-2-aziridinecarboxylate esters in excellent yields.

A convenient automated solid-phase synthesis of PNA-(5′)-DNA-(3′)-PNA chimera

An automated online solid-phase synthesis of Ac-cac ct T∗GG TC t∗ac ct-Gly-OH1 using standard DNA and appropriately protected PNA building blocks (2–5) is described. This chimera forms stable duplexes with complementary DNA and RNA.

An approach towards the synthesis of oligomers containing a N-2-hydroxyethyl-aminomethylphosphonate backbone: A novel PNA analogue

A convenient route to the preparation of 4-methoxy-1-oxido-pyridine-2-methyl N-2-(4,4′-dimethoxytrityloxy)ethyl-N-thymin-1-yl-aminomethylphosphonate (1a, T∗) and the corresponding N4-benzoylcytosin-1-yl derivative 1b (C∗) is reported. These PPNA monomers proved to be suitable building blocks in a solid-support synthesis of the tetradecameric fragment (C∗T∗T∗T∗C∗T∗T∗T∗T∗C∗T∗C∗T∗)dT.

A convenient approach toward the preparation of nucleopeptides

Abstract The use of the 2-nitrophenylsulfenyl group for the protection of the N-terminus of peptides and the exocyclic-amino function of deoxyadenosine will be illustrated in the assemblage of the nucleopeptides H-Phe-Tyr (pATAT)-NH2 and H-Ala-Ser(pATAT)-Ala-OAllyl via phospho- and phosphitetriester intermediates.

A Convenient and General Approach to the Synthesis of Properly Protected d-Nucleoside-3′-hydrogenphosphonates via Phosphite Intermediates.

Aus den Nucleosiden (I) entstehen mit dem Salicyl-chlorphosphit (II) die Substitutionsprodukte (III), die mit Pyridin/ Wasser zu den Phosphonaten (IV) reagieren.

Automated Chemical Synthesis of PNA and PNA-DNA Chimera on a Nucleic Acid Synthesizer

Abstract Automated chemical synthesis of PNA and PNA-DNA chimera on a DNA synthesizer using the monomethoxytrityl/acyl protecting group strategy is described.

SYNTHESIS OF A NUCLEOPEPTIDE FRAGMENT FROM POLIOVIRUS GENOME

Abstract Condensation of a properly protected uridylylated nucleopeptide with a heptadecapeptide gives after one-step deprotection the target nucleopeptide H-Gly-Ala-Tyr( 5′ pU)-Thr-Gly-Leu-Pro-Asn-Lys-Lys-Pro-Asn-Val-Pro-Thr-Ile-Arg-Thr-Ala-Lys-Val-Gln-OH.

Mild basic and highly selective hydrolysis of an aryl-alkyl 1-H-phosphonate diester: Preparation of the mono-1-H-phosphonylated dipeptide Z-ser(OPO2H2)-tyr(OH)NH2.

Abstract Basic hydrolysis (pyridine-water) of a 2,2,2-trifluoroethyl tyrosinyl 1-H-phosphonate diester affords predominantly a 2,2,2-trifluoroethyl 1-H-phosphonate mono-ester and tyrosine. The latter finding has been applied to the synthesis of a dipeptide consisting of a 1-H-phosphonylated serine and a non-1-H-phosphonylated tyrosine moiety.