1999' 5' 21 by S' J' Kim

1
1999. 5. 21 by S. J. Kim
2
1. PA-catalyzed enzymatic reaction mechanism
(1) Mechanism
1 D-a-phenylglycine methyl ether 2 POM-6-APA
(RCH2OCOC(CH3)3), 6-APA(RH) 3 pivampicillin
(RCH2OCOC(CH3)3), ampicillin(RH) 4
D-a-phenylglycine
3
1. PA-catalyzed enzymatic reaction mechanism
(2) Mechanism on PA
Pingpong bibi mechanism
4
2. The reason why we use organic solvent

• Increasing solubility of water-soluble
  substrate. e.g. aromatic compound, ahcohol,
  steroid
• Prevent by-product e.g. unwanted hydrolysis
• By adjusting pK value and lowering water
  activity, it can shift thermodynamic
  equilibrium of reactions.

5
3. Experimental results

• All expectation are broken, slower reaction
  rate, lower yield.
• More experiment showed that organic solvent
  affect PA directly.
• Critical variables are electrophobicity of
  organic solvents and electrostatic interaction
  between active site of PA and organic solvents.

6
4. Properties of organic solvents

• Size and shape
• Charge, dipole and dielectric constantBy
  using CHEM OFFICE PRO

7
5. Preliminary material
Governing equation
In inside of particle
In outside of particle
Boundary condition
At surface
8
5. Preliminary material
BEM formulation
At surface
where
9
5. Preliminary material
Some problem stated in last seminar

• Reducing elements number
• Charge assign
• Active site by Swissmodel

10
6. Potential field of PA

• Finding optimal plane for active site
• Various pH, k, e valuesview with TECPLOT

11
6. Future work

• Calculation of binding energy with PA and
  solvent particle by using UHBD
• Brownian dynamics