The use of Fmoc-Lys(Pac)-OH and penicillin G acylase in the preparation of novel semisynthetic insulin analogs

Lenka Zakova; Daniel Zyka; Jan Jezek; Ivona Hanclova; Miloslav Sanda; Andrzej M. Brzozowski; Jiri Jiracek

doi:10.1002/psc.847

The use of Fmoc-Lys(Pac)-OH and penicillin G acylase in the preparation of novel semisynthetic insulin analogs

Lenka Zakova, Daniel Zyka, Jan Jezek, Ivona Hanclova, Miloslav Sanda, Andrzej M. Brzozowski, Jiri Jiracek

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

In this paper, we present the detailed synthetic protocol and characterization of Fmoc-Lys(Pac)-OH, its use for the preparation of octapeptides H-Gly-Phe-Tyr-N-MePhe-Thr-Lys(Pac)-Pro-Thr-OH and H-Gly-Phe-Phe-His-Thr-Pro-Lys(Pac)-Thr-OH by solid-phase synthesis, trypsin-catalyzed condensation of these octapeptides with desoctapeptide(B23-B30) -insulin, and penicillin G acylase catalyzed cleavage of phenylacetyl (Pac) group from N'-amino group of lysine to give novel insulin analogs [TyrB25, N-MePheB26, LysB28, ProB291 -insulin and [HisB261 -insulin. These new analogs display 4 and 78% binding affinity respectively to insulin receptor in rat adipose membranes. Copyright (C) 2007 European Peptide Society and John Wiley & Sons, Ltd.

Original language	English
Pages (from-to)	334-341
Number of pages	8
Journal	JOURNAL OF PEPTIDE SCIENCE
Volume	13
Issue number	5
DOIs	https://doi.org/10.1002/psc.847
Publication status	Published - May 2007

Keywords

insulin analogs
semisynthesis
phenylacetyl
penicillin G acylase
PROTECTING GROUP TECHNIQUES
SOLID-PHASE SYNTHESIS
PEPTIDE-SYNTHESIS
B-CHAIN
AMINO-ACIDS
BIOLOGICAL-ACTIVITY
COUPLING REAGENTS
ENZYMATIC REMOVAL
B26-30 INSULIN
C-TERMINUS

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10.1002/psc.847

Cite this

@article{70b69709ed7c4177839b5a4d46b99328,

title = "The use of Fmoc-Lys(Pac)-OH and penicillin G acylase in the preparation of novel semisynthetic insulin analogs",

abstract = "In this paper, we present the detailed synthetic protocol and characterization of Fmoc-Lys(Pac)-OH, its use for the preparation of octapeptides H-Gly-Phe-Tyr-N-MePhe-Thr-Lys(Pac)-Pro-Thr-OH and H-Gly-Phe-Phe-His-Thr-Pro-Lys(Pac)-Thr-OH by solid-phase synthesis, trypsin-catalyzed condensation of these octapeptides with desoctapeptide(B23-B30) -insulin, and penicillin G acylase catalyzed cleavage of phenylacetyl (Pac) group from N'-amino group of lysine to give novel insulin analogs [TyrB25, N-MePheB26, LysB28, ProB291 -insulin and [HisB261 -insulin. These new analogs display 4 and 78% binding affinity respectively to insulin receptor in rat adipose membranes. Copyright (C) 2007 European Peptide Society and John Wiley & Sons, Ltd.",

keywords = "insulin analogs, semisynthesis, phenylacetyl, penicillin G acylase, PROTECTING GROUP TECHNIQUES, SOLID-PHASE SYNTHESIS, PEPTIDE-SYNTHESIS, B-CHAIN, AMINO-ACIDS, BIOLOGICAL-ACTIVITY, COUPLING REAGENTS, ENZYMATIC REMOVAL, B26-30 INSULIN, C-TERMINUS",

author = "Lenka Zakova and Daniel Zyka and Jan Jezek and Ivona Hanclova and Miloslav Sanda and Brzozowski, {Andrzej M.} and Jiri Jiracek",

year = "2007",

month = may,

doi = "10.1002/psc.847",

language = "English",

volume = "13",

pages = "334--341",

journal = "JOURNAL OF PEPTIDE SCIENCE",

issn = "1075-2617",

publisher = "Wiley-Blackwell",

number = "5",

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T1 - The use of Fmoc-Lys(Pac)-OH and penicillin G acylase in the preparation of novel semisynthetic insulin analogs

AU - Zakova, Lenka

AU - Zyka, Daniel

AU - Jezek, Jan

AU - Hanclova, Ivona

AU - Sanda, Miloslav

AU - Brzozowski, Andrzej M.

AU - Jiracek, Jiri

PY - 2007/5

Y1 - 2007/5

N2 - In this paper, we present the detailed synthetic protocol and characterization of Fmoc-Lys(Pac)-OH, its use for the preparation of octapeptides H-Gly-Phe-Tyr-N-MePhe-Thr-Lys(Pac)-Pro-Thr-OH and H-Gly-Phe-Phe-His-Thr-Pro-Lys(Pac)-Thr-OH by solid-phase synthesis, trypsin-catalyzed condensation of these octapeptides with desoctapeptide(B23-B30) -insulin, and penicillin G acylase catalyzed cleavage of phenylacetyl (Pac) group from N'-amino group of lysine to give novel insulin analogs [TyrB25, N-MePheB26, LysB28, ProB291 -insulin and [HisB261 -insulin. These new analogs display 4 and 78% binding affinity respectively to insulin receptor in rat adipose membranes. Copyright (C) 2007 European Peptide Society and John Wiley & Sons, Ltd.

AB - In this paper, we present the detailed synthetic protocol and characterization of Fmoc-Lys(Pac)-OH, its use for the preparation of octapeptides H-Gly-Phe-Tyr-N-MePhe-Thr-Lys(Pac)-Pro-Thr-OH and H-Gly-Phe-Phe-His-Thr-Pro-Lys(Pac)-Thr-OH by solid-phase synthesis, trypsin-catalyzed condensation of these octapeptides with desoctapeptide(B23-B30) -insulin, and penicillin G acylase catalyzed cleavage of phenylacetyl (Pac) group from N'-amino group of lysine to give novel insulin analogs [TyrB25, N-MePheB26, LysB28, ProB291 -insulin and [HisB261 -insulin. These new analogs display 4 and 78% binding affinity respectively to insulin receptor in rat adipose membranes. Copyright (C) 2007 European Peptide Society and John Wiley & Sons, Ltd.

KW - insulin analogs

KW - semisynthesis

KW - phenylacetyl

KW - penicillin G acylase

KW - PROTECTING GROUP TECHNIQUES

KW - SOLID-PHASE SYNTHESIS

KW - PEPTIDE-SYNTHESIS

KW - B-CHAIN

KW - AMINO-ACIDS

KW - BIOLOGICAL-ACTIVITY

KW - COUPLING REAGENTS

KW - ENZYMATIC REMOVAL

KW - B26-30 INSULIN

KW - C-TERMINUS

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DO - 10.1002/psc.847

M3 - Article

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