Optimized Fmoc-Removal Strategy to Suppress the Traceless and Conventional Diketopiperazine Formation in Solid-Phase Peptide Synthesis

被引：8

作者：

Yang, Yi ^{[1
]}

Hansen, Lena ^{[1
]}

机构：

[1] Ferring Pharmaceut AS, Chem Dev, Global Pharmaceut R&D, DK-2770 Kastrup, Denmark

来源：

ACS OMEGA | 2022年 / 7卷 / 14期

关键词：

CIS-TRANS ISOMERIZATION; AMINO-ACIDS;

D O I：

10.1021/acsomega.2c00214

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

DKP (diketopiperazine) formation is a ubiquitous side reaction in SPPS (solid-phase peptide synthesis) that is highly sequence-dependent. Secondary amino acids are extremely prone to host such a side reaction. DKP formation is predominantly induced at the Fmoc (fluorenylmethyloxycarbonyl)-removal step mediated by a secondary amine, which conventionally employs piperidine/DMF (dimethylformamide). In this study, alternative Fmoc-removal solution 2% DBU (1,8-diazabicyclo[5.4.0]undec-7-ene)/5% piperazine/NMP (N-methyl-2-pyrrolidone) led to drastic DKP reduction relative to 20% piperidine/DMF.

引用

页码：12015 / 12020

页数：6

共 16 条

[1] Use of N-tritylamino acids and PyAOP(1) for the suppression of diketopiperazine formation in Fmoc/(t)Bu solid-phase peptide synthesis using alkoxybenzyl ester anchoring linkages
Alsina, J
Giralt, E
Albericio, F
[J]. TETRAHEDRON LETTERS, 1996, 37 (24) : 4195 - 4198
[2] BARLOS K, 1991, INT J PEPT PROT RES, V37, P513
[3] THE 9-FLUORENYLMETHYLOXYCARBONYL FAMILY OF BASE-SENSITIVE AMINO-PROTECTING GROUPS
CARPINO, LA
[J]. ACCOUNTS OF CHEMICAL RESEARCH, 1987, 20 (11) : 401 - 407
[4] CELMA C, 1992, PEPTIDE RES, V5, P62
[5] Solid-phase synthesis of a cyclodepsipeptide: Cotransin
Coin, Irene
Beerbaum, Monika
Schmieder, Peter
Bienert, Michael
Beyermann, Michael
[J]. ORGANIC LETTERS, 2008, 10 (17) : 3857 - 3860
[6] Cis-trans isomerization of omega dihedrals in proteins
Craveur, Pierrick
Joseph, Agnel Praveen
Poulain, Pierre
de Brevern, Alexandre G.
Rebehmed, Joseph
[J]. AMINO ACIDS, 2013, 45 (02) : 279 - 289
[7] SOLID-PHASE PEPTIDE-SYNTHESIS UTILIZING 9-FLUORENYLMETHOXYCARBONYL AMINO-ACIDS
FIELDS, GB
NOBLE, RL
[J]. INTERNATIONAL JOURNAL OF PEPTIDE AND PROTEIN RESEARCH, 1990, 35 (03): : 161 - 214
[8] Fragment Condensation of C-Terminal Pseudoproline Peptides without Racemization on the Solid Phase
Heinlein, Christian
Silva, Daniel Varon
Troester, Andrea
Schmidt, Jasmin
Gross, Angelina
Unverzagt, Carlo
[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2011, 50 (28) : 6406 - 6410
[9] p-Nitrobenzyloxycarbonyl (pNZ) as a temporary Nα-protecting group in orthogonal solid-phase peptide synthesis -: Avoiding diketopiperazine and aspartimide formation
Isidro-Llobet, A
Guasch-Camell, J
Alvarez, M
Albericio, F
[J]. EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2005, 2005 (14) : 3031 - 3039
[10] Cis-trans peptide variations in structurally similar proteins
Joseph, Agnel Praveen
Srinivasan, Narayanaswamy
de Brevern, Alexandre G.
[J]. AMINO ACIDS, 2012, 43 (03) : 1369 - 1381

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