Peptide synthesis : Part 10. Use of pentafluorophenyl esters of fluorenylmethoxycarbonylamino acids in solid phase peptide synthesis

The application of fluorenylmethoxycarbonyl-amino-acid pentafluorophenyl esters to solid phase peptide synthesis under polar reaction conditions is described. Reaction rates are increased in the presence of l-hydroxybenzotriazole. The technique is illustrated by preparation of decapeptide and dodecapeptide sequences.     

亲水性二苯甲胺树脂制备及用于肽合成研究

通过反相悬浮共聚合成了含酯基的聚丙烯酰胺树脂, 再经乙二胺取代和两步缩合反应引入二苯甲胺功能基团。讨论了反应条件对各步反应的影响。测定了该载体与几种保护氨基酸的缩合率并合成了模型肽。缩合率和模型肽的纯度都令人满意。     

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

2-Hydroxyethylsulfonylmethyl-substituted polystyrenes are obtained from Merrifield's 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.     

Caged O-phosphorothioyl amino acids as building blocks for Fmoc-based solid phase peptide synthesis

The synthesis of 1-(2-nitrophenylethyl) caged O-phosphorothioylserine, -threonine, and -tyrosine derivatives is reported. These amino acid building blocks can be directly incorporated into peptides by Fmoc-based solid phase synthesis as their pentafluorophenyl esters or as symmetric anhydrides. Upon irradiation with UV light, the thiophosphate group, representing a hydrolysis resistant phosphate analog, is revealed.     

Preparation of N(G)-substituted L-arginine analogues suitable for solid phase peptide synthesis

A high-yielding and concise preparation of N(G)-substituted L-arginine analogues, suitably protected for use in solid phase peptide synthesis, is reported. The synthesis of each analogue employed an activated thiourea intermediate that was converted under mild conditions to the desired L-arginine analogue (10 examples, each in near quantitative yield). Subsequent allyl group removal provided each analogue in a form ideally suited for use in solid phase peptide synthesis.     

Solid-phase peptide synthesis in water. Part 3: A water-soluble N-protecting group, 2-[phenyl(methyl)sulfonio]ethoxycarbonyl tetrafluoroborate, and its application to solid phase peptide synthesis in water

Chemical synthesis of peptides has been performed in various organic solvents, but the safe disposal of organic solvents is now an important environmental issue. Our aim is to be able to perform solid-phase peptide synthesis in water. For this, we have designed a new water-soluble N-protecting group, 2-[phenyl(methyl)sulfonio]ethoxycarbonyl (Pms), and have studied its introduction onto amino acids. Pms-amino acids were prepared by treating 2-(phenylthio)ethoxycarbonyl amino acids with methyl iodide in the presence of silver tetrafluoroborate. Because sulfur-containing amino acids, such as Met and Cys, were modified by the reaction, we designed a new reagent, 2-[phenyl(methyl)sulfonio]ethyl-4-nitrophenyl carbonate, to introduce the Pms group on amino acids. This reagent is a stable crystalline material and its introduction onto amino acids (including sulfur-containing amino acids) was successful. The solid-phase synthesis of Leu- and Met-enkephalin amides using Pms-protected amino acids was successfully achieved in water.     

Preparation of ribonucleoside 3′-O-phosphoramidites and their application to the automated solid phase synthesis of oligonucleotides

Oligoribonucleotides, six to fifteen units long, were synthesized on a controlled pore glass support using ribonucleoside 3′-O-phosphoramidite reagents. Average coupling yields of up to 98% were obtained with diisopropylaminophosphoramidite derivatives. fa]Some preliminary results of this work have been communicated by N. Usman & K.K. Ogilvie at the CIC-AIC Conference June 1984, Montreal, Canada.     

Fmoc solid phase synthesis of polyamides containing pyrrole and imidazole amino acids

[structure: see text]. Polyamides containing N-methylimidazole (Im) and N-methylpyrrole (Py) amino acids are synthetic ligands that have an affinity and specificity for DNA comparable to those of many naturally occurring DNA binding proteins. A machine-assisted Fmoc solid phase synthesis of polyamides has been optimized to afford high stepwise coupling yields (>99%). Two monomer building blocks, Fmoc-Py acid and Fmoc-Im acid, were prepared in multigram scale. Cleavage by aminolysis followed by HPLC purification affords up to 200 mg quantities of polyamide with purities and yields greater than or equal to those reported using Boc chemistry. A broader set of reaction conditions will increase the number and complexity of minor groove binding polyamides which may be prepared and help ensure compatibility with many commercially available peptide synthesizers.     

Preparation of trimethylsilyl derivatives of amino acids and peptides for peptide synthesis

Russian Chemical Bulletin -     

Basic techniques of working on a solid phase: From ABC of the peptide synthesis to libraries of non-natural amino acids

Libraries of hardly available amino acids bearing a heteroaromatic ring (2-pyrimidyl, substituted 2-pyridyl or 2-thiazolyl) at the amino group were prepared using solid-phase synthesis on various resins. The synthesized compounds are structurally similar to some known antidiabetic drugs. The paper combines features of a review (elementary introduction to the solid-phase synthesis methodology and technique for beginners and selected methods from peptide chemistry) and step-by-step experimental protocols (tested by the authors) useful as a methodic tool. The presented protocols (immobilization and modification of amino acids, placing and removal of common protective groups) require no sophisticated equipment and may be useful as pictorial introductory tasks for students education.     

2-(4-Sulfophenylsulfonyl)ethoxycarbonyl group: a new water-soluble N-protecting group and its application to solid phase peptide synthesis in water

Solid phase peptide synthesis is carried out in organic solvents, creating environmental problems after disposal. To avoid this problem, we aimed to perform solid phase peptide synthesis in water. A new water-soluble N-protecting group, 2-(4-sulfophenylsulfonyl)ethoxycarbonyl (Sps) group, was designed and Sps-amino acids were prepared. To evaluate the utility of this technique, Leu-enkephalin amide was prepared by solid phase synthesis using Sps-amino acids in water.     

Preparation and application of new acid labile anchor groups for the synthesis of peptide amides by FMOC solid phase synthesis

The synthesis and application of new linkage agents for the preparation of peptide amides using a modified Fmoc strategy is described.     

Pyruvoyl, a novel amino protecting group on the solid phase peptide synthesis and the peptide condensation reaction

In one of the peptide condensation methods termed thioester method, an amino protecting group is required in the lysine side chain. In this study, to investigate the efficiency of the pyruvoyl group as an amino protecting group, we synthesized N^α-fluorenylmethoxycarbonyl (Fmoc)-N^ε-pyruvoyl-lysine and introduced it into peptides and glycopeptides by the ordinary Fmoc-based solid phase peptide synthesis. The pyruvoyl peptide could be condensed with a peptide thioester by the thioester method, and this protecting group was easily removed by o-phenylenediamine treatment without significant side reactions.     

Modular nucleic acid surrogates. Solid phase synthesis of alpha-helical peptide nucleic acids (alpha PNAs)

[formula: see text] The synthesis and characterization of prototype alpha-helical peptide nucleic acid (alpha PNA) modules 1-3 as well as disulfide dimers 4 and 5 are reported. These molecules combine an alpha-helical peptidyl scaffold with well-defined nucleobase molecular recognition patterns and could serve as a basis for novel antisense and/or antigene agents. Structure assignments for these alpha PNAs were supported by MALDI-TOF mass spectrometry, and the alpha-helical nature of 4 in water was confirmed by circular dichroism (CD) spectroscopy.