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The Study of New Type Casomorphin on Its Design,Synthesis, Selection and Structure-activity

Author: ZhangShuZuo
Tutor: WuLei
School: Tianjin University of Commerce
Course: Fermentation Engineering
Keywords: New type Casomorphins Design Synthesis Active Analgesic Simulation
CLC: TQ464.7
Type: Master's thesis
Year: 2011
Downloads: 23
Quote: 0
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Abstract


Opioid peptides, also known as sedative anesthesia peptide, it is a nerve-active substance, a hormone and neurotransmitter function in the central nervous system and peripheral organs can function. It can be divided into endogenous opioid peptides and exogenous opioid peptides. Endogenous opioid peptides can be produced by the body itself in some special cases, human needs, thereby regulating human emotions. Exogenous opioid peptides derived from food and substandard material, which milk is the main source of exogenous opioid peptides. Laboratory has previously obtained from the enzymatic hydrolysis of casein, having the opioid activity of a new piece of casomorphin, having the sequence: YFYPELFRQFYQLDA, molecular weight: 2252.48. The laboratory synthesis the casomorphins sequence, through animal experiments was: have a similar utility of casomorphin and enzymatic synthesis casomorphins analgesic and anti-fatigue. On this basis, the topic for the mother to the casomorphins sequence substitution principle, according to the charge distribution and similar structures, rational design of novel casomorphin. Were: (1) NH 2 -Tyr-Phe-Trp-Pro-Glu-Leu-Phe-Arg-Gln-Phe-Tyr-Gln-Leu-Asp-Ala-OH; (2 ) NH 2 -Tyr-Phe-Phe-Pro-Glu-Leu-Phe-Arg-Gln-Phe-Tyr-Gln-Leu-Asp-Ala-OH; (3) NH 2 -Tyr-Gly-Tyr-Pro-Glu-Leu-Phe-Arg-Gln-Phe-Tyr-Gln-Leu-Asp-Ala-OH; (4) NH 2 -Tyr-Phe-Tyr-Pro-Glu-Leu-Phe-Arg-Gln-Phe-Tyr-Gln-Leu-OH; (5) NH 2 -Tyr-Phe-Tyr-Pro- Glu-Leu-Phe-Arg-Gln-Phe-OH; (6) NH 2 -Tyr-Phe-Tyr-Pro-Glu-Leu-Phe-Arg-OH. Known through laboratory solid phase peptide synthesis method, the final consolidated synthesis of new casomorphin average yield of 56.86%. Order to compare this project designed the six kinds the new casomorphins original enzymatic casomorphins for peptide the original synthesis casomorphins bioactive peptide, the subject of using analgesic experiments and peripheral analgesic experiments to detect. The results show that: the synthesis of novel casomorphin have analgesic and peripheral analgesic effects. (1) - (4) of the overall analgesic effect than the original synthetic casomorphins good, but not good as its stability. (5), (6) as a original casomorphins analgesic effect. Comprehensive the two analgesic experimental, eventually may have a new casomorphin opioid activity from strong to weak as follows: (4) gt; (3) gt; (2) gt; (1), (6) gt; (5). The adoption sybyl6.92 on six samples spatial structure, its receptor docking simulations, can be more reasonable interpretation of the above results. Simulation results show that: (1), (2), (6) Sample No. can be combined with the μ receptor selectivity; (3), (5), samples can be combined with the κ receptor selectivity; No. (4) samples can be combined with the δ receptor selectivity. Only (3), No. (4) is more successful in receiving the cavity they receptor activity. This also with the detection result of the animal experiment (3), (4) the activity of the sample No. strong consistent.

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CLC: > Industrial Technology > Chemical Industry > Pharmaceutical chemical industry > Drug production of biological products > Amino acids,peptides,proteins
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