Difficulties in coupling to conformationally constrained aromatic amino acids

Z. Bozso, G. Toth, R. F. Murphy, Sándor Lovas

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Coupling of amino acids to 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) and 1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid (HOTic) is difficult. In model experiments, use of 1-hydroxy-7-azabenzotriazole (HOAt) in combination with either N,N-diisopropylcarbodiimide (DIC) or O-(7-azabenzotriazol-1-yl)-1,1,3,3-Tetramethyluronium (HATU) for activation was effective in solving coupling difficulties. Based on this finding, HOTic was then incorporated into the 20-31 fragment of human epidermal growth factor (hEGF). [Abu20,31,HOTic22]hEGF(20-31)-NH2 was shown to be a 'difficult sequence', but replacement of the Tyr at position 29 with HOTic facilitates the complete dodecapeptide synthesis. Abbreviations: Tic, 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid; HOTic, 1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid; HBTU, 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate; BOP, benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate; PyBrop, bromo-tris(pyrrolidino)phosphonium hexafluorophosphate; DCC, N,N-dicyclohexylcarbodiimide; DIC, N,N-diisopropylcarbodiimide; HOBt, 1-hydroxybenzotriazole; HOAt, 1-hydroxy-7-azabenzotriazole; HATU, O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate; hEGF, human epidermal growth factor; Boc, t-butyloxycarbonyl; OtBu, t-butyloxy; Bzl, benzyl; OBzl, benzyloxy; 2ClZ, 2-chlorobenzyloxycarbonyl; Fmoc, fluorenylmethyloxycarbonyl; pMBHA, 4-methylbenzhydrylamine; NMP, N-methylpyrrollidinone; DCM, dichloromethane; DMF, N,N-dimethylformamide; DMSO, dimethyl sulfoxide; THF, tetrahydrofuran; DIEA, N,N-diisopropylethylamine; TFA, trifluoroacetic acid; TFMSA, trifluoromethanesulfonic acid; DMS, dimethyl sulfide; HPLC, high-performance liquid chromatography; ACN, acetonitrile.

Original languageEnglish
Pages (from-to)157-163
Number of pages7
JournalLetters in Peptide Science
Volume7
Issue number3
DOIs
StatePublished - 2000

Fingerprint

Aromatic Amino Acids
Carboxylic acids
Epidermal Growth Factor
Amino acids
Carboxylic Acids
Dimethyl Sulfoxide
High Pressure Liquid Chromatography
Dicyclohexylcarbodiimide
Trifluoroacetic Acid
Dimethylformamide
Methylene Chloride
High performance liquid chromatography
Trifluoroacetic acid
Dimethyl sulfoxide
Dichloromethane
Acetonitrile
Chemical activation
Amino Acids
Acids
1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Difficulties in coupling to conformationally constrained aromatic amino acids. / Bozso, Z.; Toth, G.; Murphy, R. F.; Lovas, Sándor.

In: Letters in Peptide Science, Vol. 7, No. 3, 2000, p. 157-163.

Research output: Contribution to journalArticle

Bozso, Z. ; Toth, G. ; Murphy, R. F. ; Lovas, Sándor. / Difficulties in coupling to conformationally constrained aromatic amino acids. In: Letters in Peptide Science. 2000 ; Vol. 7, No. 3. pp. 157-163.
@article{a8425e003d014ea694e9fe25501f7dda,
title = "Difficulties in coupling to conformationally constrained aromatic amino acids",
abstract = "Coupling of amino acids to 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) and 1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid (HOTic) is difficult. In model experiments, use of 1-hydroxy-7-azabenzotriazole (HOAt) in combination with either N,N-diisopropylcarbodiimide (DIC) or O-(7-azabenzotriazol-1-yl)-1,1,3,3-Tetramethyluronium (HATU) for activation was effective in solving coupling difficulties. Based on this finding, HOTic was then incorporated into the 20-31 fragment of human epidermal growth factor (hEGF). [Abu20,31,HOTic22]hEGF(20-31)-NH2 was shown to be a 'difficult sequence', but replacement of the Tyr at position 29 with HOTic facilitates the complete dodecapeptide synthesis. Abbreviations: Tic, 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid; HOTic, 1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid; HBTU, 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate; BOP, benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate; PyBrop, bromo-tris(pyrrolidino)phosphonium hexafluorophosphate; DCC, N,N-dicyclohexylcarbodiimide; DIC, N,N-diisopropylcarbodiimide; HOBt, 1-hydroxybenzotriazole; HOAt, 1-hydroxy-7-azabenzotriazole; HATU, O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate; hEGF, human epidermal growth factor; Boc, t-butyloxycarbonyl; OtBu, t-butyloxy; Bzl, benzyl; OBzl, benzyloxy; 2ClZ, 2-chlorobenzyloxycarbonyl; Fmoc, fluorenylmethyloxycarbonyl; pMBHA, 4-methylbenzhydrylamine; NMP, N-methylpyrrollidinone; DCM, dichloromethane; DMF, N,N-dimethylformamide; DMSO, dimethyl sulfoxide; THF, tetrahydrofuran; DIEA, N,N-diisopropylethylamine; TFA, trifluoroacetic acid; TFMSA, trifluoromethanesulfonic acid; DMS, dimethyl sulfide; HPLC, high-performance liquid chromatography; ACN, acetonitrile.",
author = "Z. Bozso and G. Toth and Murphy, {R. F.} and S{\'a}ndor Lovas",
year = "2000",
doi = "10.1023/A:1008928404072",
language = "English",
volume = "7",
pages = "157--163",
journal = "International Journal of Peptide Research and Therapeutics",
issn = "1573-3149",
publisher = "Springer Netherlands",
number = "3",

}

TY - JOUR

T1 - Difficulties in coupling to conformationally constrained aromatic amino acids

AU - Bozso, Z.

AU - Toth, G.

AU - Murphy, R. F.

AU - Lovas, Sándor

PY - 2000

Y1 - 2000

N2 - Coupling of amino acids to 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) and 1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid (HOTic) is difficult. In model experiments, use of 1-hydroxy-7-azabenzotriazole (HOAt) in combination with either N,N-diisopropylcarbodiimide (DIC) or O-(7-azabenzotriazol-1-yl)-1,1,3,3-Tetramethyluronium (HATU) for activation was effective in solving coupling difficulties. Based on this finding, HOTic was then incorporated into the 20-31 fragment of human epidermal growth factor (hEGF). [Abu20,31,HOTic22]hEGF(20-31)-NH2 was shown to be a 'difficult sequence', but replacement of the Tyr at position 29 with HOTic facilitates the complete dodecapeptide synthesis. Abbreviations: Tic, 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid; HOTic, 1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid; HBTU, 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate; BOP, benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate; PyBrop, bromo-tris(pyrrolidino)phosphonium hexafluorophosphate; DCC, N,N-dicyclohexylcarbodiimide; DIC, N,N-diisopropylcarbodiimide; HOBt, 1-hydroxybenzotriazole; HOAt, 1-hydroxy-7-azabenzotriazole; HATU, O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate; hEGF, human epidermal growth factor; Boc, t-butyloxycarbonyl; OtBu, t-butyloxy; Bzl, benzyl; OBzl, benzyloxy; 2ClZ, 2-chlorobenzyloxycarbonyl; Fmoc, fluorenylmethyloxycarbonyl; pMBHA, 4-methylbenzhydrylamine; NMP, N-methylpyrrollidinone; DCM, dichloromethane; DMF, N,N-dimethylformamide; DMSO, dimethyl sulfoxide; THF, tetrahydrofuran; DIEA, N,N-diisopropylethylamine; TFA, trifluoroacetic acid; TFMSA, trifluoromethanesulfonic acid; DMS, dimethyl sulfide; HPLC, high-performance liquid chromatography; ACN, acetonitrile.

AB - Coupling of amino acids to 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) and 1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid (HOTic) is difficult. In model experiments, use of 1-hydroxy-7-azabenzotriazole (HOAt) in combination with either N,N-diisopropylcarbodiimide (DIC) or O-(7-azabenzotriazol-1-yl)-1,1,3,3-Tetramethyluronium (HATU) for activation was effective in solving coupling difficulties. Based on this finding, HOTic was then incorporated into the 20-31 fragment of human epidermal growth factor (hEGF). [Abu20,31,HOTic22]hEGF(20-31)-NH2 was shown to be a 'difficult sequence', but replacement of the Tyr at position 29 with HOTic facilitates the complete dodecapeptide synthesis. Abbreviations: Tic, 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid; HOTic, 1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid; HBTU, 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate; BOP, benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate; PyBrop, bromo-tris(pyrrolidino)phosphonium hexafluorophosphate; DCC, N,N-dicyclohexylcarbodiimide; DIC, N,N-diisopropylcarbodiimide; HOBt, 1-hydroxybenzotriazole; HOAt, 1-hydroxy-7-azabenzotriazole; HATU, O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate; hEGF, human epidermal growth factor; Boc, t-butyloxycarbonyl; OtBu, t-butyloxy; Bzl, benzyl; OBzl, benzyloxy; 2ClZ, 2-chlorobenzyloxycarbonyl; Fmoc, fluorenylmethyloxycarbonyl; pMBHA, 4-methylbenzhydrylamine; NMP, N-methylpyrrollidinone; DCM, dichloromethane; DMF, N,N-dimethylformamide; DMSO, dimethyl sulfoxide; THF, tetrahydrofuran; DIEA, N,N-diisopropylethylamine; TFA, trifluoroacetic acid; TFMSA, trifluoromethanesulfonic acid; DMS, dimethyl sulfide; HPLC, high-performance liquid chromatography; ACN, acetonitrile.

UR - http://www.scopus.com/inward/record.url?scp=0033636531&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033636531&partnerID=8YFLogxK

U2 - 10.1023/A:1008928404072

DO - 10.1023/A:1008928404072

M3 - Article

VL - 7

SP - 157

EP - 163

JO - International Journal of Peptide Research and Therapeutics

JF - International Journal of Peptide Research and Therapeutics

SN - 1573-3149

IS - 3

ER -