Highly efficient synthesis of peptides by rational utilization of novel coupling reagents

The efficiency of different peptide coupling reagents, including carbodiimides, HOBt or HOAt-derived uronium, phosphonium and immonium salts, halouronium, halophosphonium, 2-halopyridinium and 2-halothiazolium salts, was evaluated. The synthetic strategy for coded peptides and nonribosomal peptides was discussed with an emphasis on the rational selection of peptide coupling reagents.

A NOVEL COUPLING REAGENT(PENTAFLUOROPHENYL DIPHENYLPHOSPHPATE)FOR THE PEPTIDE SYNTHESIS

Pentafluorophenyl diphenylphosphate was found to be a novel convenient coupling reagent for the peptide synthesis with several advantages.Higher yield and lower racemization were found with this reagent than DCCI.

Application of an Organophosphorus Compound-DEPBT as Coupling Reagent in Liquid Phase Peptide Synthesis

DEPBT, a novel coupling reagent containing phosphorus, was used in synthesis of pentapeptide Boc-Ile-Asn-Met-Trp(For)-Gly.OMe by solution method.

Preparation and Characterization of Super-paramagnetic Nano-beads for DNA Isolation

Unique coupling reagent, bis-(2-hydroxyethyl methacrylate) phosphate was used to prepare coated and functionalized superparamagnetic nanobeads, leading to a simple, effective method for coating the nanobeads. With this method, the thickness of the coating layer and the functional group contents on the nano-beads could be controlled by changing the quantity of the coated monomers. The nanobeads were characterized by means of transmission electron microscopy (TEM) and Fourier transformation infrared spectroscopy (FTIR). The carboxyl-modified magnetic nano-beads were employed to streamline the protocol of isolation of genomic DNA from the human whole blood.

Solid Phase Peptide Synthesis of Fusukang for AIDS

A 36-residue peptide is designed to cure acquired immunodeficiency syndrome(AIDS), and is synthesized by the manual solid phase peptide synthesis technique. Different reaction conditions of the synthesis process were discussed. Stirring efficiency of mechanics and nitrogen was compared. The mechanical method displays a predominant performance. Although the coupling efficiencies of diisopropylcarbodiimide(DIC) and dicyclohexylcarbodiimide(DCC) are virtually identical, DIC offers several advantages over DCC in practice due to different physical characters. Wash conditions after deprotection and coupling were investigated to monitor washing efficiency. 0.369 2 g crude peptide was obtained.

Peptide synthesis using pentafluorophenyl diphenylphosphate (FDP) as coupling reagent

Comparison of the reaction speed and yield with its analogues and some conventional peptide coupling reagents, pentafluorophenyl diphenylphosphate (FDP) was shown to be a more preferable ''active ester'' type reagent for the peptide synthesis. The synthesis of oligopeptides using FDP was achieved with high yields. The influences of several reaction parameters such as solvent, base, additive and temperature on the coupling reaction were studied using HPLC method. The degree of racemization with FDP determined by HPLC or Young test was shown to be lower than that of DCCI. Octapeptide Gly-Cys(Bzl)-Ser-Gly-Lys-Leu-Ile-Cys(Bzl)-OH, corresponding to the amino acid sequence of gp41 of HIV-1, was successfully synthesized by 5+3 approach using FDP with high yield.

Novel immonium type peptide coupling reagent: 5-(1H-benzotriazol-1-yloxy)-3,4-dihydro-l-methyl 2H-pyrrolium hexachloroantimonate (BDMP )

A novel immonium type coupling reagent, 5-(1H-benzotria-zol-1-yloxy )-3,4-dihydro-1-methyl 2H-pyrrolium hexachlo-roantimonate (BDMP) has been designed, synthesized and u-tilized to synthesize oligopeptides and biologically active pep-tide both in solution and solid phase with satisfactory yield, low racemization and fast reaction rate. The estimation of racemization and the influence of several reaction parameters were studied by HPLC method using the model reaction: Z-Gly-Phe-OH + Val-OMe·HCl→Z-Gly-D/L-Phe-Val-OMe. It was shown that the reactivity of BDMP was much higher and the racemization was much lower than those of HOBt-based 'onium' reagents, even though its analogues BOMI. To further verified the effectiveness of BDMP, Leu-enkephalin was synthesized both in solution and solid phase using BDMP as coupling reagent. The proposed mechanism was also speculated.

Application of DEPBT on the Synthesis of the Protected Dipeptides Containing Histidine with Unprotected Imidazole Group by Solution Method

3-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one (DEPBT) was an organophosphorus coupling reagent developed by our group. It was an effective coupling reagent for the synthesis of protected peptides containing Tyr, Ser and Thr with unprotected hydroxy group on their side chain. The further study of the synthesis of a series of protected dipeptides containing histi-dine with unprotected imidazole group using DEPBT is reported. During the synthetic procedure, the imidazole group of his-tidine did not need to be protected. When the carboxyl components were N-protected aromatic amino acids or basic amino acids, the yields were relatively high (63%-81%). However, when the carboxyl components were N -protected acidic amino acids, the yields were relatively low (47%-48%). The results expanded the application of DEPBT on the synthesis of bioactive peptides containing histidine.