Sandbox Reserved 198: Difference between revisions
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The peptide ligation chemistry in addition to solid-phase peptide synthesis is used to synthesize relatively longer peptide molecules with typical length of 125 residues<ref>David J. Boerema, Valentina. A. T., Stephen B. H. Kent, "Total Synthesis by Modern chemical Ligation Methods and High Resolution (1.1-A) X-ray structure of Ribonuclease A. Biopolymers. 2008;90(3):278-86.</ref>. The ligation methods overcome the length limitation of solid-phase synthesis, because the chemical ligation involves the joining of mutually reactive peptide segments created by solid-phase synthesis. The peptide bond in ligation is formed between an unprotected peptide and a peptide-thioester<ref>David J. Boerema, Valentina. A. T., Stephen B. H. Kent, "Total Synthesis by Modern chemical Ligation Methods and High Resolution (1.1-A) X-ray structure of Ribonuclease A. Biopolymers. 2008;90(3):278-86.</ref>. The shorter peptide segments are more rapidly prepared and are less susceptible to solubility issues in longer peptide chains. | The peptide ligation chemistry in addition to solid-phase peptide synthesis is used to synthesize relatively longer peptide molecules with typical length of 125 residues<ref>David J. Boerema, Valentina. A. T., Stephen B. H. Kent, "Total Synthesis by Modern chemical Ligation Methods and High Resolution (1.1-A) X-ray structure of Ribonuclease A. Biopolymers. 2008;90(3):278-86.</ref>. The ligation methods overcome the length limitation of solid-phase synthesis, because the chemical ligation involves the joining of mutually reactive peptide segments created by solid-phase synthesis. The peptide bond in ligation is formed between an unprotected peptide and a peptide-thioester<ref>David J. Boerema, Valentina. A. T., Stephen B. H. Kent, "Total Synthesis by Modern chemical Ligation Methods and High Resolution (1.1-A) X-ray structure of Ribonuclease A. Biopolymers. 2008;90(3):278-86.</ref>. The shorter peptide segments are more rapidly prepared and are less susceptible to solubility issues in longer peptide chains. | ||
The <scene name='Sandbox_Reserved_198/Fully_synthetic/1'>Fully Synthetic RNase A</scene> (124 residues) is prepared by two consecutive sets of one-pot ligations and related chemical transformations of six peptide segments (residues <scene name='Sandbox_Reserved_198/1-25/1'>1-25</scene>, <scene name='Sandbox_Reserved_198/26-39/1'>26-39</scene>, <scene name='Sandbox_Reserved_198/40-64/1'>40-64</scene>, <scene name='Sandbox_Reserved_198/65-83/1'>65-83</scene>, <scene name='Sandbox_Reserved_198/84-94/1'>84-94</scene>, <scene name='Sandbox_Reserved_198/95-124/1'>95-124</scene>)<ref>David J. Boerema, Valentina. A. T., Stephen B. H. Kent, "Total Synthesis by Modern chemical Ligation Methods and High Resolution (1.1-A) X-ray structure of Ribonuclease A. Biopolymers. 2008;90(3):278-86.</ref>,which can prevent undesired byproduct formation. The six unprotected peptide segments were synthesized by highly optimized, stepwise solid-phase synthesis. This synthetic pathway is simple, has high overall yields, and it eliminate the need for the isolation of intermediate products. | The <scene name='Sandbox_Reserved_198/Fully_synthetic/1'>Fully Synthetic RNase A</scene> (124 residues) is prepared by two consecutive sets of one-pot ligations and related chemical transformations of six peptide segments (residues <scene name='Sandbox_Reserved_198/1-25/1'>1-25</scene>, <scene name='Sandbox_Reserved_198/26-39/1'>26-39</scene>, <scene name='Sandbox_Reserved_198/40-64/1'>40-64</scene>, <scene name='Sandbox_Reserved_198/65-83/1'>65-83</scene>, <scene name='Sandbox_Reserved_198/84-94/1'>84-94</scene>, <scene name='Sandbox_Reserved_198/95-124/1'>95-124</scene>, as highlighted in red)<ref>David J. Boerema, Valentina. A. T., Stephen B. H. Kent, "Total Synthesis by Modern chemical Ligation Methods and High Resolution (1.1-A) X-ray structure of Ribonuclease A. Biopolymers. 2008;90(3):278-86.</ref>,which can prevent undesired byproduct formation. The six unprotected peptide segments were synthesized by highly optimized, stepwise solid-phase synthesis. This synthetic pathway is simple, has high overall yields, and it eliminate the need for the isolation of intermediate products. | ||
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1. Introduction to Ribonuclease A by Raines: http://www.uta.edu/faculty/sawasthi/Enzymology-4351-5324/Class%20Syllabus%20Enzymology/ribonucleaseA.pdf | 1. Introduction to Ribonuclease A by Raines: http://www.uta.edu/faculty/sawasthi/Enzymology-4351-5324/Class%20Syllabus%20Enzymology/ribonucleaseA.pdf | ||
2. Introduction to Peptide Synthesis: http://en.wikipedia.org/wiki/Solid_phase_peptide_synthesis#Solid-phase_synthesis | 2. Introduction to Peptide Synthesis: http://en.wikipedia.org/wiki/Solid_phase_peptide_synthesis#Solid-phase_synthesis | ||
3.Solid Phase Synthesis by Merrifield (Nobel Prize Winner):http://nobelprize.org/nobel_prizes/chemistry/laureates/1984/merrifield-lecture.pdf | 3. Solid Phase Synthesis by Merrifield (Nobel Prize Winner):http://nobelprize.org/nobel_prizes/chemistry/laureates/1984/merrifield-lecture.pdf | ||
4. Chemical Synthesis of Proteins:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845543/?tool=pmcentrez | 4. Chemical Synthesis of Proteins:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845543/?tool=pmcentrez | ||
5. Refined Crystal Structure: http://www.ncbi.nlm.nih.gov/pubmed/3680234 | 5. Refined Crystal Structure: http://www.ncbi.nlm.nih.gov/pubmed/3680234 | ||
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