Fmoc-amino Acid Research Articles

Synthesis of peptide amides by Fmoc-solid-phase peptide synthesis and acid labile anchor groups.

The preparation and use of new anchor groups for the synthesis of peptide amides by solid-phase peptide synthesis employing the Fmoc-method is described. Based on the structure of the 4,4'-dimethoxybenzhydryl group (Mbh) handles were developed, which could be cleaved by mild acid treatment to give carboxamides. The syntheses and application of Fmoc-amino-acid-(4-carboxylatomethyloxyphenyl-4'-methoxyphenyl) methyl amide and Fmoc-(4-carboxylatopropyloxyphenyl-4'-methoxyphenyl) methyl amide are described in detail. These handles were coupled to resins and a stepwise elongation of peptide chains proceeded smoothly with N alpha-9-fluorenylmethoxycarbonyl (Fmoc) amino acid derivatives using a carbodiimide/HOBt mediated reaction. The final cleavage of side-chain protecting groups and the release of the C-terminal amide moiety was achieved by the treatment with trifluoroacetic acid, dichloromethane in the presence of scavengers. Various peptides, such as the Leu-enkephalin amide and Leu-Gly-Gly-Gly-Gln-Gly-Lys-Val-Leu-Gly-NH2, which is a good substrate for F XIII, were prepared in high yields and purities.

Solid-phase synthesis of phosphopeptides.

We report the solid-phase synthesis of peptides containing O-phosphoserine. Coupling was with commercially available Fmoc-amino acid pentafluorophenyl esters, with base used at each cycle to cleave Fmoc. Phosphorylation of those serine residues left unprotected on the peptide-resin was achieved with dibenzylphosphochloridate, and finally trifluoroacetic acid was used to remove side-chain protecting groups (including the benzyl groups used for the phosphate), and to cleave the peptide from the resin in the same step. This synthetic strategy enables the preparation of peptides with individual, selectively phosphorylated residues. Alternative approaches to introduce protected phosphate and continue with coupling of further amino acids were less advantageous due to the lability of the phosphate group to base and to steric hindrance.

Peptide synthesis by a combination of solid-phase and solution methods IV minimum-racemization coupling of n α-9-fluorenylmethyloxycarbonyl amino acids to alkoxy benzyl alcohol type resins

The cesium salts of N α-9-fluorenylmethyloxycarbonyl (Fmoc) amino acids couple smoothly to new chloro derivatives of alkoxy benzyl alcohol resins. While high loading is attained under mild reaction conditions racemization can be suppressed even with Cys and His derivatives.

Darstellung geschützter peptid-fragmente unter einsatz substituierter triphenylmethyl-harze

Substituted triphenylmethyl(trityl) resins have been tested for their applicability for the synthesis of protected peptide fragments. Among them the 2-chlorotrityl resin 3c fulfills all requirements needed to obtain the desired fragments in high yield and purity, using Fmoc-amino acids protected at their side chains with groups of the t-butyl type. Graphic

Advances in ultra‐high load polymer‐supported peptide synthesis with phenolic supports: 1. A selectively‐labile c‐terminal spacer group for use with a base‐mediated n‐terminal deprotection strategy and fmoc amino acids

AbstractCrosslinked poly(N‐[2‐(4‐hydroxphenyl)ethyl]‐acrylamide) has been modified by conversion of each pendant 4‐hydroxyphenyl group to its 2‐(4‐hydroxymethyl‐phenoxy)ethanoyl‐L‐prolyl ester. This provides a spacer group which makes the polymer matrix suitable for solid (gel) phase peptide synthesis with Fmoc amino acids at ultra‐high load (2.2 mmol g−1 of spacer‐modified support). The selectively labile linkages incorporated in the spacer group provide for peptide detachment by either mild acidolysis or hydrazinolysis. The products of hydrazinolysis of intermediate and final peptide‐matrix assemblies are amenable to analysis by high‐pressure liquid chromatography (HPLC).

Peptide synthesis. Part 12. 3,4-Dihydro-4-oxo-1,2,3-benzotriazin-3-yl esters of fluorenylmethoxycarbonyl amino acids as self-indicating reagents for solid phase peptide synthesis

The preparation and characterisation of 3,4-dihydro-4-oxo-1,2,3-benzotriazinyl esters (1) of Fmoc-amino acids and their use in solid phase peptide synthesis is described. Ionisation of the liberated hydroxy component (2) by the starting resin-bound amine provides a useful colour indicator of the progress of acylation reactions.

Improved solid-phase synthesis of bombesin by continuous flow procedure using fmoc amino acids

Improved solid-phase synthesis of bombesin by continuous flow procedure using fmoc amino acids

Synthesis, conformation, and biological activity of the carbohydrate-free vespulakinin 1.

Synthesis of the carbohydrate-free heptadecapeptide corresponding to the amino acid sequence of vespulakinin 1 was achieved by the continuous flow solid phase procedure on 4-hydroxymethyl-phenoxyacetyl-norleucyl derivatized Kieselguhr-supported polydimethylacrylamide resin, as well as by a combination of solid phase and solution syntheses. Preformed Fmoc-amino acid symmetrical anhydrides (Boc derivative for the N-terminal residue) were used for amine acylation in the continuous flow method. Serine and threonine were side chain protected as tert.-butyl ethers and the 4-methoxy-2, 3, 6,-trimethyl-benzenesulfonyl group was used for masking the guanidino function of arginine residues. After cleavage from the resin the final peptide was purified by ion exchange chromatography and characterized by amino acid analysis, high voltage electrophoresis, and RP-HPLC analysis. Alternatively, the protected N-terminal octapeptide, Fmoc-Thr(But)-Ala-Thr(But)-Thr(But)-Arg(Mtr)-Arg-(Mtr)-Arg(Mtr)-Gly-OH was prepared on 4-hydroxymethyl-3-methoxyphenoxyacetyl-norleucyl derivatized Kieselguhr-supported polydimethylacrylamide resin and the C-terminal nonapeptide H-Arg(NO2)-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-(NO2)-OBzl was synthesized in solution through the fragment condensation method. The two fragments were coupled by the DCC-HOBt procedure and the resulting heptadecapeptide was deblocked and purified. The conformational features of the synthesized peptides are reported. Preliminary pharmacological experiments indicated that carbohydrate-free vespulakinin 1 is more potent than bradykinin in lowering rat blood pressure.

ChemInform Abstract: ((9‐Fluorenylmethyl)oxy)carbonyl (Fmoc) Amino Acid Chlorides. Synthesis, Characterization, and Application to the Rapid Synthesis of Short Peptide Segments.

AbstractSynthesis and properties of a series of Fmoc‐amino acid chlorides (X) are described as outlined in the reaction scheme.

An improved method for anchoring of 9-fluorenylmethoxycarbonyl-amino acids to 4-alkoxybenzyl alcohol resins.

Esterification of Fmoc-amino acids to 4-alkoxybenzyl alcohol polystyrene by 2,6-dichlorobenzoyl chloride represents a convenient method. It is free of the two side-reactions observed with dicyclohexylcarbodiimide/ 4-dimethylaminopyridine, viz. racemization and dipeptide formation.

Quantitative analysis of amino acids in conifer tissues by high-performance liquid chromatography and fluorescence detection of their 9-fluorenylmethyl chloroformate derivatives

Pre-column derivatization of amino acids in conifer extracts to form 9-fluorenylmethyl formate (FMOC) esters and the subsequent reversed-phase high-performance liquid chromatography (HPLC) analysis of these esters have been investigated. Qualitative analysis of putative FMOC-amino acid derivative HPLC peaks from a pine extract was performed by gas chromatography-mass spectrometry in order to confirm their identities. The precision, measured with ten replicate extracts, ranged from 2.2 to 15.6%. Theoretical responses from standards and extracts were compared with the actual response as an assay for systematic errors. The detector response was investigated as a function of the ratio amino acid/reagent and the range of linearity for each amino acid was established. The method is suitable for analysis of amino acids in crude extracts of small samples of Scots pine tissues, and for simultaneous determination of primary and secondary amino acids.

Convergent solid phase peptide synthesis vi : synthesis by the fmoc procedure with a modified protocol of two protected segments, sequence 5-17 and 18-31 of the neurotoxin ii of the scorpion androctonus australis hector.

Synthesis of two protected peptides thirteen and fourteen residues long, sequence 5-17, i.e. Fmoc-Tyr(cHex)- Ile-Val-Asp(Bzl)-Asp(Bzl)-Val-Asn-Cys(Acm)-Thr(Bzl)-Tyr(cHex)- Phe-Cys(Acm)-Gly-OH, and 18-31, i.e. Fmoc-Arg (Tos)-Asn-Ala- Tyr(cHex)-Cys(Acm )-Asn-Glu(Bzl)-Glu(Bzl)-Cys(Acm)-Thr(Bzl)- Lys(Z)-Leu-Lys(Z)-Gly-OH, of the scorpion neurotoxin II from Androctonus australis Hector , was performed by the solid phase method. The hydroxymethylphenoxymethyl copoly(styrene - 1% -divinylbenzene) type resin was used in combination with Fmoc-amino acids for both syntheses. A general protocol minimizing side reactions has been developed for the use of the base labile Fmoc-α-amino protecting group. The time of reaction with piperidine (50% in N,N'-dimethylformamide) has been shortened to three times one minute and coupling was performed mainly in methylene chloride with just dicyclohexyl or diisopropyl-carbodiimide. The side chain protecting groups of the Fmoc-α-amino acids were of the hydrogen fluoride labile type, which permitted, after trifluoroacetic acid cleavage of the peptide to resin ester bond, obtainment of protected peptides. The crude segments, precipitated from N,N'-dime- thylacetamide with water, were highly purified by HPLC and chemically characterized for future use in convergent solid phase assembling.

ChemInform Abstract: Rapid and Efficient Method for the Preparation of Fmoc‐Amino Acids Starting from 9‐Fluorenylmethanol.

Chemischer InformationsdienstVolume 17, Issue 39 Natural Products ChemInform Abstract: Rapid and Efficient Method for the Preparation of Fmoc-Amino Acids Starting from 9-Fluorenylmethanol. P. B. W. TEN KORTENAAR, P. B. W. TEN KORTENAARSearch for more papers by this authorB. G. VAN DIJK, B. G. VAN DIJKSearch for more papers by this authorM. PEETERS, M. PEETERSSearch for more papers by this authorB. J. RAABEN, B. J. RAABENSearch for more papers by this authorP. J. H. M. ADAMS, P. J. H. M. ADAMSSearch for more papers by this authorG. I. TESSER, G. I. TESSERSearch for more papers by this author P. B. W. TEN KORTENAAR, P. B. W. TEN KORTENAARSearch for more papers by this authorB. G. VAN DIJK, B. G. VAN DIJKSearch for more papers by this authorM. PEETERS, M. PEETERSSearch for more papers by this authorB. J. RAABEN, B. J. RAABENSearch for more papers by this authorP. J. H. M. ADAMS, P. J. H. M. ADAMSSearch for more papers by this authorG. I. TESSER, G. I. TESSERSearch for more papers by this author First published: September 30, 1986 https://doi.org/10.1002/chin.198639328AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume17, Issue39September 30, 1986 RelatedInformation

(Fluoren-9-ylmethoxy)carbonyl (Fmoc) amino acid chlorides. Synthesis, characterization, and application to the rapid synthesis of short peptide segments

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT(Fluoren-9-ylmethoxy)carbonyl (Fmoc) amino acid chlorides. Synthesis, characterization, and application to the rapid synthesis of short peptide segmentsLouis A. Carpino, Beri J. Cohen, Kenton E. Stephens Jr., S. Yahya Sadat-Aalaee, Jien Heh Tien, and Denton C. LangridgeCite this: J. Org. Chem. 1986, 51, 19, 3732–3734Publication Date (Print):September 1, 1986Publication History Published online1 May 2002Published inissue 1 September 1986https://doi.org/10.1021/jo00369a042RIGHTS & PERMISSIONSArticle Views3954Altmetric-Citations156LEARN 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 (467 KB) Get e-Alerts Get e-Alerts

Rapid and efficient method for the preparation of Fmoc‐amino acids starting from 9‐fluorenylmethanol

A method is presented for the high‐yield synthesis of Fmoc amino acids, which precludes racemization and over‐reaction due to carboxyl activation. A detailed procedure is given for the preparation of Fmoc‐ONSu.

Diketopiperazine formation in solid phase peptide synthesis using p-alkoxybenzyl ester resins and Fmoc-amino acids

Summary Diketopiperazine formation rates under the usual conditions of a solid phase peptide synthesis cycle with Fmoc-amino acids have been studied on a p -alkoxybenzyl ester resin. Piperidine has been found to be an extremely efficient catalyst for the intramolecular aminolysis reaction.

ChemInform Abstract: SUPPRESSION OF SIDE‐REACTIONS DURING THE ATTACHMENT OF FMOC‐AMINO ACIDS TO HYDROXYMETHYL POLYMERS

Two side-reactions occur during the DCC-mediated attachment of Fmoc-amino acids to p-alkoxybenzyl alcohol resins viz. dipeptide formation and racemization. The addition of 1-hydroxybenzotriazole in combination with a low reaction temperature is shown to decrease both side-reactions to an acceptable level without lowering the degree of incorporation.

Solid phase peptide synthesis using Nα-fluorenylmethoxycarbonylamino acid pentafluorophenyl esters

Fmoc-amino acid pentafluorophenyl esters have been used successfully in the synthesis of a difficult decapeptide sequence using a polar reaction medium and resin support.

Application of N,N-dimethylformamide dineopentyl acetal for efficient anchoring of N alpha-9-fluorenylmethyloxycarbonylamino acids as p-alkoxybenzyl esters in solid-phase peptide synthesis.

The attachment of Fmoc-amino acids onto p- alkoxybenzyl alcohol resins via DCC-DMAP coupling suffers from two different problems: formation of dimers and racemization. The use of N,N-dimethylformamide dineopentyl acetal for the preparation of Fmoc- aminoacyloxybenzyl handles is the basis of a safe and efficient anchoring method that avoids both problems.

STABLE ISOLATED SYMMETRICAL ANHYDRIDES OF Nα‐9‐FLUORENYLMETHYLOXYCARBONYLAMINO ACIDS IN SOLID‐PHASE PEPTIDE SYNTHESIS:

The synthesis and isolation of symmetrical anhydrides of N alpha-9-fluorenylmethyloxycarbonyl (Fmoc) amino acids using water soluble carbodiimide is described. These compounds were used in a solid phase peptide synthesis of methionine-enkephalin on a p-benzyloxybenzyl ester polystyrene 1% divinylbenzene resin support. Homogeneous free pentapeptide was obtained in 42% overall yield. The Fmoc amino acid symmetrical anhydrides were stable during prolonged storage (2 years of 0 degrees) and offer advantages over present "Fmoc solid phase" methods which use anhydrides formed in situ.