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Studies on enzymatic peptide synthesis in biphasic aqueous-organic systems with product extraction

Untersuchungen zur enzymatischen Peptidsynthese in biphasischen wä\rig-organischen Systemen mit Produktextraktion

  • Organische Chemie Und Biochemie
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Abstract

The dipeptide derivativesZ-Tyr-Leu-NH2 andMca-Tyr-Leu-NH2 were synthesized by α-chymotrypsin-catalyzed coupling reactions in solvent systems consisting of buffer and ethyl acetate. In comparison to a pure aqueous medium, in which only insignificant synthesis takes place, the product formation is greatly enhanced in a biphasic medium due to extraction of the dipeptide into the organic phase. The influence of several reaction parameters, such as buffer concentration, reaction time, volume ratio of organic and aqueous phase, and reagent concentration on the yield ofZ-Tyr-Leu-NH2 was investigated. Replacement of the hydrophobicZ-group by the more hydrophilic chloroacetyl group resulted in better dipeptide yields at higher reaction rates.

Zusammenfassung

Die DipeptidderivateZ-Tyr-Leu-NH2 undMca-Tyr-Leu-NH2 wurden durch α-chymotrypsin-katalysierte Kupplung in biphasischen Systemen aus Puffer und Essigsäureethylester hergestellt. Im Vergleich zu einem rein wäßrigen Medium, in dem nahezu keine Synthese erfolgt, wird in einem biphasischen System die Synthesereaktion durch Extraktion des Dipeptids in die organische Phase wesentlich begünstigt. Es wurde der Einfluß verschiedener Reaktionsparameter, wie Pufferkonzentration, Reaktionszeit, Volumenverhältnis von organischer zu wäßriger Phase und Reaktandenkonzentration auf die Ausbeute anZ-Tyr-Leu-NH2 untersucht. Ein Austausch der hydrophobenZ-Gruppe gegen die hydrophilere Chloracetylgruppe führte zu besseren Dipeptidausbeuten bei höheren Reaktionsgeschwindigkeiten.

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Authors and Affiliations

  1. Sektion Biowissenschaften, Bereich Biochemie, Karl-Marx-Universität, DDR-7010, Leipzig, German Democratic Republic

    Peter Kuhl, Regina Schaaf & Hans-Dieter Jakubke

Authors
  1. Peter Kuhl
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  2. Regina Schaaf
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  3. Hans-Dieter Jakubke
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Additional information

Abbreviations: IUPAC-IUB rules for peptides are followed, see Eur J Biochem 27: 201 (1972).Ac = acetyl,Glt = 4-carboxybutyryl (glutaryl),Mca = monochloroacetyl,Z = benzyloxycarbonyl, −OMe = methyl ester, −Nan = 4-nitroanilide, TLC = thin layer chromatography. All amino acids are ofL-configuration.

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Kuhl, P., Schaaf, R. & Jakubke, HD. Studies on enzymatic peptide synthesis in biphasic aqueous-organic systems with product extraction. Monatsh Chem 118, 1279–1288 (1987). https://doi.org/10.1007/BF00816870

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  • DOI: https://doi.org/10.1007/BF00816870

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