Tresyl-Mediated Synthesis:  Kinetics of Competing Coupling and Hydrolysis Reactions as a Function of pH, Temperature, and Steric Factors

Kinetic parameters have been measured for coupled nucleophilic and solvolytic reactions of 2,2,2-trifluoroethanesulfonyl (tresyl)-modified poly(ethylene glycol) based on a system of coupled differential equations implied by recently proposed elementary reaction mechanisms. Fitted kinetic parameters...

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Bibliographic Details
Published in:Bioconjugate chemistry 1999-03, Vol.10 (2), p.213-220
Main Authors: Sperinde, Jeffrey J, Martens, Benjamin D, Griffith, Linda G
Format: Article
Language:English
Subjects:
Algorithms
Dipeptides - chemistry
Hydrogen-Ion Concentration
Hydrolysis
Indicators and Reagents
Isomerism
Kinetics
Lysine - analogs & derivatives
Lysine - chemistry
Phenylalanine - chemistry
Polyethylene Glycols
Structure-Activity Relationship
Sulfones
Thermodynamics
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Summary:Kinetic parameters have been measured for coupled nucleophilic and solvolytic reactions of 2,2,2-trifluoroethanesulfonyl (tresyl)-modified poly(ethylene glycol) based on a system of coupled differential equations implied by recently proposed elementary reaction mechanisms. Fitted kinetic parameters were found to be strong functions of pH, temperature, and steric factors. To maximize the total yield of coupled amine as well as the fraction of secondary amine linkages, our model predicts that it is desirable to run tresyl coupling reactions at low temperatures at pH ∼8.0, depending on the amine pK a for primary, unhindered amines. For branched primary amines, our data favor room temperature at a slightly higher pH.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc980070j