Solid-phase Synthesis Of Protected Peptides Research Articles

The (2-phenyl-2-trimethylsilyl)ethyl-(PTMSEL)-linker in the synthesis of glycopeptide partial structures of complex cell surface glycoproteins.

The (2-phenyl-2-trimethylsilyl)ethyl-(PTMSEL) linker represents a novel fluoride-sensitive anchor for the solid-phase synthesis of protected peptides and glycopeptides. Its cleavage is achieved under almost neutral conditions using tetrabutylammonium fluoride trihydrate in dichloromethane thus allowing the construction of complex molecules sensitive to basic and acidic media commonly required for the cleavage of standard linker systems. The advantages of the PTMSEL linker are demonstrated in the synthesis of glycopeptides from the liver intestine (LI)-cadherin and the mucin MUC1, bearing carbohydrate moieties such as N-linked chitobiose or O-linked sialyl-T(N)-residues. The synthesis of these types of glycopeptides is difficult because they are prone to secondary structure formation during the synthesis on the solid phase as well as in the completely deprotected form. Using the PTMSEL linker these molecules are accessible by automated synthesis according to the Fmoc strategy without frequently observed side reactions such as aspartimide or diketopiperazine formation.

15] Convergent solid-phase peptide synthesis

Publisher Summary This chapter discusses solid-phase synthesis and coupling of protected peptides. There are two main strategies for the chemical synthesis of peptides: (1) chain elongation in linear synthesis is carried out by repetitive N α amino group deprotection and protected amino acid coupling steps, (2) convergent synthesis involves the synthesis and coupling of protected peptide segments. Both strategies can be carried out in solution or on a solid support, although solution and solid-phase methodologies can coexist in convergent synthesis. Protected peptide segments can be elaborated on solid supports and coupled in solution or vice versa. Convergent solid-phase peptide synthesis (CSPPS) involves (1) solidphase synthesis of protected peptides (these must retain the protecting groups of the N α -amino and the side-chain functions after cleavage from the resin), (2) purification and characterization of the protected peptides, and (3) their solid-phase coupling.

ChemInform Abstract: Amino Acids and Peptides. Part 38. Development of a New Amino- Protecting Group, 2-Adamantyloxycarbonyl, and Its Application to Peptide Synthesis.

A new Iµ-amino protecting group, 2-adamantyloxycarbonyl (2-Adoc), was developed, and its application to the solid-phase synthesis of protected peptides was demonstrated in combination with Nα-fluoren-9-ylmethoxycarbonyl (Fmoc) protection and trifluoroacetic acid (TFA)-cleavable resin support. The 2-Adoc group was applied successfully also to the solution-phase peptide synthesis depending on tert-butoxycarbonyl (Boc)-chemistry.

Amino acids and peptides. Part 38. Development of a new amino-protecting group, 2-adamantyloxycarbonyl, and its application to peptide synthesis

A new Iµ-amino protecting group, 2-adamantyloxycarbonyl (2-Adoc), was developed, and its application to the solid-phase synthesis of protected peptides was demonstrated in combination with Nα-fluoren-9-ylmethoxycarbonyl (Fmoc) protection and trifluoroacetic acid (TFA)-cleavable resin support. The 2-Adoc group was applied successfully also to the solution-phase peptide synthesis depending on tert-butoxycarbonyl (Boc)-chemistry.

Solid-phase synthesis of protected peptides using new cobalt(III) ammine linkers.

Cobalt(III) ammine complexes of the type cis-[CoL4(4-AMB)O-AA-Boc](CF3SO3)2, where L4 = bisethylenediamine (en)2 or tetraammine (NH3)4, and 4-AMB = 4-(aminomethyl)benzoic acid, have been synthesized and used as linkers to polystyrene resins for solid-phase synthesis of protected peptides. Boc/t-Bu-protected [Leu5]enkephalin was assembled on the two different Co(III) resins, and then cleaved from the resins by reduction of the Co(III) center in 93-96% yield. HPLC-purified protected [Leu5]enkephalin was obtained in 67-69% overall yield and characterized by amino acid analysis and 1H NMR. Stepwise synthesis on the Co(en)2-resin was also used in the assembly of Boc-Asp(OcHex)-Arg(Mts)-Gly-Asp(OcHex)-Ala-Pro-Lys(2Cl-Z)-Gl y-OH, a sequence from collagen alpha 1 Type 1. The protected peptide was cleaved from the Co(III) resin in 74% yield, and the HPLC-purified nonapeptide was characterized by amino acid analysis, 1H NMR and liquid secondary-ion mass spectrometry (LSIMS). New routes are described for the synthesis of isomerically pure Co(III) anchor complexes. The Co(III) resins were found to be compatible with both the tert-butyloxycarbonyl (Boc) and the 9-fluorenylmethoxycarbonyl (Fmoc) N alpha-protecting group strategies used in solid-phase peptide synthesis.

Development of a new amino-protecting group, 2-adamantyloxycarbonyl (2-adoc), and its application to the solid-phase synthesis of protected peptides

A new ε-amino protecting group, 2-adamantyloxycarbonyl (2-Adoc) has been developed, and its application to the solid phase synthesis of the protected peptide has been demonstrated successfully in combination with Nα-fluoren-9-ylmethoxycarbonyl (Fmoc) protection and trifluoroacetic acid (TFA)-cleavable resin support.

A new flourene-derived anchor for solid-phase synthesis of protected peptides

N-[9-(hydroxymethyl)-2-fluorenyl succinamic acid may be used as an anchoring linkage for the preparation of protected peptide segments in combination with Boc/Bzl 1 protection scheme. The new handle proved to be stable to the usual conditions of solid-phase peptide synthesis and gave the protected peptide in high yields and purities by treatment with piperidine or morpholine.

Solid-phase synthesis of peptides using allylic anchoring groups. An investigation of their palladium-catalysed cleavage

The use of two different allylic “handles” has been investigated in the solid-phase synthesis of protected peptides. Very high yields for the cleavage of peptides from the resin, under mild conditions which preserve side-chain protecting groups can be achieved by carrying out the cleavage reaction in 2:2:1 THF/DMSO/0.5 M HCl, using morpholine as nucleophile and Pd(Ph 3P) 4 as catalyst.

NPE-resin, a new approach to the solid-phase synthesis of protected peptides and oligonucleotides II. Synthesis of protected peptides

The use of a polymer support containing the base-labile 2-(2-nitrophenyl)ethyl (NPE) handle allows the preparation of fully protected (Boc/Bzl) peptides, which may be used for the Convergent Solid-Phase Peptide Synthesis of large peptides or proteins.

NPE-resin, a new approach to the solid-phase synthesis of protected peptides and oligonucleotides I : Synthesis of the supports and their application to oligonucleotide synthesis.

The preparation of polymeric supports containing a base labile 2-(2-nitrophenyl) ethyl linkage and the attachment of protected nucleosides is described together with their application to oligonucleotide synthesis.

A novel solvent system for solid-phase synthesis of protected peptides: the disaggregation of resin-bound antiparallel .beta.-sheet

This paper reports the application of the solvent system of lithium bromide in tetrahydrofuran for the disaggregation of protected peptide bound to the Kaiser oxime resin. Fourier-transform infrared spectroscopy is used to characterize the aggregating structure and to follow the disaggregation. The solvation of resin-bound peptide has practical consequences in that the yield of the nucleophilic cleavage of protected peptides from the Kaiser resin is greatly increased

Solid-phase synthesis of protected peptides on a polymer-bound oxime: preparation of segments comprising the sequence of a cytotoxic 26-peptide analog

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolid-phase synthesis of protected peptides on a polymer-bound oxime: preparation of segments comprising the sequence of a cytotoxic 26-peptide analogW. F. DeGrado and E. T. KaiserCite this: J. Org. Chem. 1982, 47, 17, 3258–3261Publication Date (Print):August 1, 1982Publication History Published online1 May 2002Published inissue 1 August 1982https://doi.org/10.1021/jo00138a011RIGHTS & PERMISSIONSArticle Views520Altmetric-Citations136LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (567 KB) Get e-Alerts Get e-Alerts

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

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 Merrifield's 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.