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Reaction And ESI-MS Studies Of Peptide Formation From Amino Acids Assisting By Phosphorus Reagents

Posted on:2005-10-02Degree:DoctorType:Dissertation
Country:ChinaCandidate:S X CaoFull Text:PDF
GTID:1101360125457317Subject:Organic Chemistry
Abstract/Summary:PDF Full Text Request
Peptide formation is one of the most important reactions in prebiotic evolution. Moreover, Phosphorus plays an important role in prebiotic evolution and in process of the life. Therefore, the investigation of peptide formation assisting by phosphorus reagents will be helpful for their mechanism opening and may elucidate the essence of the life from a special angle. In the present dissertation, using electrospray ionspray mass spectrometry (ESI-MS) and high performance liquid chromatography-mass spectrometry (HPLC-MS), we studied the mechanism of peptide formation directed by organic and inorganic phosphorus reagents. Moreover, the mass spectrometry characteristics of the related compounds were studied in detail for the structural elucidation. Some novel rearrangements were observed and there mechanisms were presumed.With the assistance of HPLC-ESI-MS/MS, the self-assembly products of serine and histidine penta-coordinated phosphorus compounds were separated and identified. The expectative product was seryl-histidine dipeptide, however, it was found that there was almost equimolar amount of histidyl-histidine dipeptide as well as seryl-histidine dipeptide. The mechanism was speculated that there was competing reaction between penta-coordinated phosphoryl serine and histidine in the reaction process. As a result, two types of dipeptide were produced.Self-assembly peptide formation directed by inorganic phosphorus reagents from amino acids was investigated in detail. Amino acids could assemble into oligo-peptides. As the reaction time was prolonged, the length of the peptides was increased. Increasing the reaction temperature, assisting by microwave, enhancing the polarity of solvent would accelerate the reaction velocity of peptide formation. The rate of peptide formation mediated by phosphorus oxychloride was apparently fasterthan assisted by phosphorus trichloride. The result showed that not only a-amino acids could assemble to oligo-peptide but P-alanine, 2-amino-2-methyl-propionic acid and 4-aminomethyl-cyclohexane carboxylic acid, which included an amino and carboxyl group simultaneously, could also produce peptide. However, the reaction rate of a-amino acids was faster than P-amino acids.According to above result and the tracking experiments of 31P-NMR, the reaction mechanisms of self-assembly peptide formation by phosphorus oxychloride activation was investigated. It was proposed that there might be two pathways for peptide formation of a-amino acids. One pathway is through the transition state of phosphoric-carboxylic anhydride. The amino group of an amino acid attacks the carbonyl group of the transition state of phosphoric-carboxylic anhydride to form peptide and lost one hydroxyl phosphorus oxychloride molecule. The other pathway is through the transition state of penta-coordinated phosphorus compound. The carbonyl group of the penta-coordinated phosphorus transition state was activated and then was attacked by an amino acid to form the peptide bond. We proposed that the self-assembly peptide formation of a-amino acids was mainly through the second pathway. However, P-amino acids and 4-aminomethyl-cyclohexane carboxylic acid could not form the penta-coordinated phosphorus transition state, so they assembled into peptides only by the first pathway.In the process of studying the peptide formation assisting by inorganic phosphorus agents, we firstly found the formation of cyclic peptides and identified the structure of them. Through optimizing the condition of the reaction, the yields of cyclic peptide were increased. The separation of cyclic peptides was also investigated in detail. Cyclic dipeptide and cyclic hexapeptide were purified from the cyclic peptide library. The construction of cyclic peptide library would enhance diversity of peptide libraries and increase the possibility of discovering new drug. Simultaneously, the new dehydration derivatives of cyclic peptide of alanine was separated andidentified to include the bridge ring unit. The studies showed that the inorganic...
Keywords/Search Tags:amino acid, phosphorus oxychloride, phosphorus trichloride, peptide formation, cyclic peptide, reaction mechanism, ESI-MS, HPLC-MS, dimolecular amino acids hydridophorane.
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