G.I. Tesser

Synthesis of 2-hydroxyethylsulfonyl-methyl-substituted polystyrenes and their application in solid phase peptide synthesis

Abstract 2-Hydroxyethylsulfonylmethyl-substituted polystyrenes are obtained from Merrifields chloromethylated, cross-linked copolymer, by treatment with sodium 2-hydroxyethylmercaptide in liquid ammonia, followed by oxidation with m-chloroperbenzoic acid. Boc-amino acids can be esterified with the polymer, using dicyclohexylcarbodiimide in dichloromethane. Further condensations are possible via conventional procedures. Protected peptide derivatives, thus prepared, can be detached from the resin by brief treatment with a base. A high elimination rate was observed when the cleavage was performed with a 0.1 M solution of sodium hydroxide containing methanol and a limited amount of water. In the absence of methanol only trace amounts of the product were liberated.

Synthesis of Chirally Pure Ornithine Based PNA Analogues

Abstract A stereoselective synthesis of a chiral PNA analogue containing an ornithine based backbone is described. In this approach each elongation cycle consists of two individual coupling steps: i.e. extension of the free δ-amino function in the growing chain by a TOPPipU mediated coupling with Fmoc-Orn(Boc)-OH, and subsequent acylation of a free α-amine with thymin-1-ylacetic acid. Thyminyl decamers were prepared following this strategy and hybridization experiments indicated that they formed stable complexes with cRNA.

Comparison of the applicability of 2-hydroxyethylsulfonylmethyl- and chloromethyl-polystyrenes in the solid-phase synthesis of protected peptides

Abstract In order to compare the applicability of resins in the preparation of protected peptides two solid-phase syntheses of a protected ACTH-(5–10)-hexapeptide have been performed, one using 2-hydroxyethylsulfonylmethyl-polystyrene and the other with Merrifields chloromethylated polystyrene. To obtain a good comparison, equivalent methods were used as far as possible. Optimal conditions for deprotection of amino groups and for the liberation of the end-product were determined. Chromatographic examination of the crude fission products of the peptidyl resins presented important clues towards the nature of the underlying fission mechanism. Using an automated peptide synthesizer the pure end-product was obtained from both resins in approximately the same yield (ca. 70%). It appeared that the isolation of the product from the suffone resin is less laborious, since the critical alkali-treatment, necessary for the liberation of the product, proceeds faster and, if properly carried out, avoids transesterification.

One-step protection of the nucleoside base in thymidine and uridine

Abstract Unprotected thymidine and uridine react with 4-nitrophenylsulfonyl ethene ( 3 ) in a base catalyzed Michael type addition to give O4-(4-nitrophenylsulfonylethyl)thymidine-( 6 ) and -uridine ( 7 ), respectively. The 4-nitrophenylsulfonylethyl group is cleaved within 2.5 hours at 50–55°C by concentrated aqueous ammonia, via β-elimination.

Stepwise solid phase synthesis of uridylylated viral genome-linked peptides using uridylylated amino acid building blocks

Abstract The uridylylated amino acid building blocks 2-cyanoethyl-(Nα-9-fluorenylmethoxy-carbonyl-tyrosin-4-yl)-(2′,3′-di-O-acetyluridin-5′-yl) phosphate and 2-chlorophenyl-(Nα-fluorenyl-methoxycarbonyl-serin-3-yl)-(2′,3′-di-O-acetyluridin-5′-yl) phosphate have been used successfully in an on-line SPPS of the VPgpU from the polio, coxsackie and cowpea mosaic virus.

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.

An expedient to solid phase Edman degradation. Synthesis and properties of 4-isothiocyanato Benzoyl-DL-homoserine lactone.

The synthesis of p-isothiocyanatobenzoylhomoserine lactone from DL-homoserine as well as from L-methionine is described. The compound constitutes a good tool in the solid phase Edman degradation of tryptic protein fragments terminated by lysine.