Enzymatic peptide synthesis in low water content systems : Preparative enzymatic synthesis of [Leu]- and [Met]-enkephalin derivatives
Clapés, Pere ; Torres, Josep Lluis and Adlercreutz, Patrick LU
(1995)
In Bioorganic and Medicinal Chemistry
3(3).
p.245-255
- Abstract
A novel total enzymatic synthesis of [Leu]- and [Met]-enkephalin derivatives was accomplished in low-water content systems at a preparative scale. α-Chymotrypsin, papain, thermolysin and bromelain adsorbed on Celite were used as catalysts. Organic solvents such as acetonitrile and ethyl acetate with small amounts of buffer added or at specific water activity were used as reaction media. Simple readily available amino acid ester derivatives were used as starting building blocks. This feature allowed the possibility of using the products in one step directly as acyl-donor ester, without any chemical or enzymatic modification, in the next enzymatic coupling. The optimal strategy for the synthesis of the enkephalin derivatives was different... (More)
A novel total enzymatic synthesis of [Leu]- and [Met]-enkephalin derivatives was accomplished in low-water content systems at a preparative scale. α-Chymotrypsin, papain, thermolysin and bromelain adsorbed on Celite were used as catalysts. Organic solvents such as acetonitrile and ethyl acetate with small amounts of buffer added or at specific water activity were used as reaction media. Simple readily available amino acid ester derivatives were used as starting building blocks. This feature allowed the possibility of using the products in one step directly as acyl-donor ester, without any chemical or enzymatic modification, in the next enzymatic coupling. The optimal strategy for the synthesis of the enkephalin derivatives was different depending on the carboxy terminal group. The preparation of the carboxy-terminal amide derivatives (R-Tyr-Gly-Gly-Phe-Leu[Met]-NH2) was achieved via 4 + 1 fragment condensation catalyzed by α-chymotrypsin. The carboxy-terminal ethyl ester derivatives (R-Tyr-Gly-Gly-Phe-Leu[Met]-OEt) were obtained via 2 + 3 condensation catalyzed by bromelain, a quite unusual protease for peptide synthesis but more effective than papain in this coupling. Both syntheses were carried out in four enzymatic steps and one or two chemical deprotection steps routinely used in peptide synthesis. The overall yields of pentapeptide derivatives were between 40-54% of pure product.
(Less)
- author
- Clapés, Pere
; Torres, Josep Lluis
and Adlercreutz, Patrick
LU
- organization
- publishing date
- 1995-01-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Bioorganic and Medicinal Chemistry
- volume
- 3
- issue
- 3
- pages
- 11 pages
- publisher
- Elsevier
- external identifiers
-
- scopus:0028965899
- pmid:7606386
- ISSN
- 0968-0896
- DOI
- 10.1016/0968-0896(95)00019-D
- language
- English
- LU publication?
- yes
- id
- 51ee6b57-109e-4826-86ef-e7da8c1a493c
- date added to LUP
- 2019-06-22 09:08:10
- date last changed
- 2024-01-01 12:15:27
@article{51ee6b57-109e-4826-86ef-e7da8c1a493c,
abstract = {{<p>A novel total enzymatic synthesis of [Leu]- and [Met]-enkephalin derivatives was accomplished in low-water content systems at a preparative scale. α-Chymotrypsin, papain, thermolysin and bromelain adsorbed on Celite were used as catalysts. Organic solvents such as acetonitrile and ethyl acetate with small amounts of buffer added or at specific water activity were used as reaction media. Simple readily available amino acid ester derivatives were used as starting building blocks. This feature allowed the possibility of using the products in one step directly as acyl-donor ester, without any chemical or enzymatic modification, in the next enzymatic coupling. The optimal strategy for the synthesis of the enkephalin derivatives was different depending on the carboxy terminal group. The preparation of the carboxy-terminal amide derivatives (R-Tyr-Gly-Gly-Phe-Leu[Met]-NH<sub>2</sub>) was achieved via 4 + 1 fragment condensation catalyzed by α-chymotrypsin. The carboxy-terminal ethyl ester derivatives (R-Tyr-Gly-Gly-Phe-Leu[Met]-OEt) were obtained via 2 + 3 condensation catalyzed by bromelain, a quite unusual protease for peptide synthesis but more effective than papain in this coupling. Both syntheses were carried out in four enzymatic steps and one or two chemical deprotection steps routinely used in peptide synthesis. The overall yields of pentapeptide derivatives were between 40-54% of pure product.</p>}},
author = {{Clapés, Pere and Torres, Josep Lluis and Adlercreutz, Patrick}},
issn = {{0968-0896}},
language = {{eng}},
month = {{01}},
number = {{3}},
pages = {{245--255}},
publisher = {{Elsevier}},
series = {{Bioorganic and Medicinal Chemistry}},
title = {{Enzymatic peptide synthesis in low water content systems : Preparative enzymatic synthesis of [Leu]- and [Met]-enkephalin derivatives}},
url = {{http://dx.doi.org/10.1016/0968-0896(95)00019-D}},
doi = {{10.1016/0968-0896(95)00019-D}},
volume = {{3}},
year = {{1995}},
}