Liquid-phase Peptide Synthesis Research Articles

Liquid-phase Peptide Synthesis by Fragment Condensation on a Soluble Polymer Support. III. The Influence of the Content and the Chain Length of a Peptide Anchored to a Soluble Polymer Support on the Reactivity of the Amino-free Terminal of the Peptide

Abstract In order to investigate the influence of the content and the chain length of a peptide anchored to a soluble polymer support on the reactivity of the amino-free terminal of the peptide, chloromethylated polystyrene, which is a starting material for peptide synthesis on a matrix, was prepared by the copolymerization of (chloromethyl)styrene with styrene. By the copolymerization, the chloromethyl content on the resin was easily controlled and obtained as reproducible. The repetitive peptide-chain elongations of a pentapeptide, –(Ala2–Leu3)–, and a decapeptide, –(Ala2–Leu3–Pro2–Leu3)–, were performed by the usual method, using soluble polymer supports with various contents of Ile–Ile, which was used as the internal reference to evaluate the coupling yields by means of amino-acid analyses of the resulting peptide resins. The solubility of the peptide resin, which depends on the content of the peptide and the solubility of the peptide fragment on the matrix, was found to be one of the important factors for an efficient coupling in liquid-phase fragment condensations on a soluble polymer support.

Liquid Phase Peptide Synthesis by the Fragment Condensation on Soluble Polymer Support. II. The Azide Method

Abstract Fragment condensation on a soluble polymer support by the azide method gave rise to the efficient coupling (94–99% yield) of an N-protected tetrapeptide azide with the amino acid anchored to the soluble polymer support. Bulkiness of amino acid residues on the polymer support did not affect the reactivity toward the peptide azide.

Cleavage of protected amino acids and peptides from the new o-nitrogenzoyl polyethylene glycol support by catalytic hydrogenolysis

Catalytic hydrogenolysis as a cleavage method for removal of protected amino acids and peptides from the 3-nitro-4-bromonethylbenzoyl polyethylene glycol support used in liquid-phase peptide synthesis is demonstrated.

Liquid Phase Peptide Synthesis by the Fragment Condensation on Soluble Polymer Support. I. Efficient Coupling and Relative Reactivity of a Peptide Fragment with Various Coupling Reagents

Abstract The fragment condensation on the soluble polymer support using dicyclohexylcarbodiimide (DCCI) plus 1-hydroxy-1H-benzotriazole (HOBt), diethoxyphosphoryl cyanide (DEPC), and triphenylphosphine (Ph3P) plus di-2-pyridyl disulfide ((PyS)2) as coupling reagents gave rise to efficient coupling (86–99% yield) of the peptide fragment, t-butyloxycarbonyl-l-O-benzyl-tyrosylglycylglycyl-l-phenylalanine [Boc-l-Tyr(Bzl)–Gly–Gly–l-Phe–OH], to the amino free terminal of Leu anchored to the soluble polymer support, H–l-Leu–OCH2–resin. Relative reactivity ratios of Boc–amino acids and Boc–l-Tyr(Bzl)–Gly–Gly-l-Phe–OH with H–l-Leu–OCH2–resin in the coupling reaction using the three coupling reagent systems could be easily determined by use of amino acid ratios in the acid hydrolysates of the resulting peptide resins in which they were taken. The peptide chain length of Boc–l-Tyr(Bzl)–Gly–Gly–l-Phe–OH has no influence on the reactivity of C-terminal amino acid in the coupling reaction using DCCI plus HOBt or DEPC as a coupling reagent when Boc–l-Phe–OH was replaced with Boc–l-Tyr(Bzl)–Gly–Gly–l-Phe–OH. The coupling reagent, Ph3P plus (PyS)2, brought about a marked decrease in the reactivity of the fragment peptide acid.

Liquid-phase method for peptide synthesis utilizing photolytic cleavage from a new o-nitrobenzoyl polyethylene glycol support

Photolysis as a method for removal of a tert-butyloxycarbonyl-protected peptide possessing a free C-terminal carboxyl group from a polystyrene support in the solid-phase method of peptide synthesis was introduced by Rich, D. H. and Gurwara, S.K. ((1975) J. Am. Chem. Soc. 97, 1575–1578). Using this basic concept we prepared a photosensitive 3-nitro-4-bromomethylbenzoyl polyethylene glycol support for use in the liquid-phase method of peptide synthesis. Photolytic cleavage of a protected tetrapeptide possessing a free C-terminal carboxyl group from the polyethylene glycol support resulted in a 98% yield compared with a 69% yield for the photolytic cleavage from the polystyrene support. This application of photolysis as a cleavage method in liquid-phase peptide synthesis avoids the low yields and rather drastic conditions needed to remove a peptide attached directly to the polyethylene glycol support in the conventional liquid-phase method.

Ribonuclease S-peptide. A model for molecular recognition.

The relationship of structure to function in the recognition of ribonuclease S-peptide by S-protein was studied by several methods. Liquid phase peptide synthesis was employed to generate analogs of S-peptide in which from 1 to 8 residues were deleted from the NH2-terminal end of the S-peptide. Additional derivatives were made by substitutions in the NH2-terminal three amino acids or by modifying the S-peptide analogs by trifluoroacetylation. The analogs were generated in the following way. S-Peptide was cleaved with chymotrypsin. The fragment obtained, RNase(9-20), was purified and lengthened step by step using liquid phase peptide synthesis. A second set of analogs were prepared by cleavage of CF3CO-S-peptide with elastase and the resulting CF3CO-RNase(7-20), similarly lengthened. The various analogs of S-peptide were tested in their capacity to combine with S-protein and regenerate biological activity as measured by Vmax and Kb. This work shows a positive contribution of every one of the first 8 NH2-terminal residues of S-peptide to the molecular recognition of S-protein in the presence of RNA substrate. Substitution of the first 3 residues by alanine or blocking of the free amino groups decreases recognition, indicating that the original primary structure is the most favorable one.

Kinetic studies of the liquid phase peptide synthesis

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTKinetic studies of the liquid phase peptide synthesisE. Bayer, M. Mutter, R. Uhmann, J. Polster, and H. MauserCite this: J. Am. Chem. Soc. 1974, 96, 23, 7333–7336Publication Date (Print):November 1, 1974Publication History Published online1 May 2002Published inissue 1 November 1974https://doi.org/10.1021/ja00830a027RIGHTS & PERMISSIONSArticle Views589Altmetric-Citations48LEARN 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 (498 KB) Get e-Alerts Get e-Alerts