Structural studies of reagents for peptide bond formation: Crystal and molecular structures of HBTU and HATU

Abdelmoty, Iman; Alberício, Fernando; Carpino, Louis A.; Foxman, Bruce M.; Kates, Steven A.

doi:10.1007/bf00126274

Cited by 104 publications

(83 citation statements)

References 16 publications

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“…Method A: A mixture of protected iminodiacetic acid (0.25 mmol), HBTU [8] (0.5 mmol) and DIEA (1 mmol) was stirred at 0 ~ for 3-5 rain in DMF (2 ml) and then added to a solution of an amino acid ester or amino acid amide hydrochloride (0.5 mmol) and DIEA (0.5 mmol) in 2 ml of DMF at 0 ~ The reaction mixture was stirred at 0 ~ for 1 h and overnight at rt. The reaction mixture was diluted with 75 ml of ethyl acetate, and the mixture was washed with 1 N HC1 (2 x 10 ml), satd NaHCO3 (2 x 10 ml), and saturated NaC1 (2 x 10 ml).…”

Section: General Methods For Activation and Coupling For The Synthesismentioning

confidence: 99%

Coupling of iminodiacetic acid with amino acid derivatives in solution and solid phase

et al. 2000

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SummaryThe IR studies for the preactivation step of N-protected iminodiacetic acid with different coupling reagents (TCFH, TFFH, HATU, HBTU, HSTU) were reported here and showed the formation of an anhydride as an active intermediate in case of TCFH and TFFH. The formation of a mixture of an anhydride and an active ester (-OBt, -OAt or -OSu) were observed for HBTU, HATU or HSTU coupling reagent. Dependent on the coupling conditions, acylation of N-protected iminodiacetic acid with amino acid ester or amide derivatives in solution phase gave monoor di-substituted iminodiacetic acid derivatives. Coupling of N-protected iminodiacetic acid with an amino acid or peptide attached to a solid support (PAL-PEG-PS or Wang resin) gave only the monosubstituted iminodiacetic acid derivatives.

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Section: General Methods For Activation and Coupling For The Synthesismentioning

confidence: 99%

Coupling of iminodiacetic acid with amino acid derivatives in solution and solid phase

et al. 2000

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“…Synthetic scheme for preparing TOMBU (17) and COMBU (18). Carpino et al [28] reported that HBTU (4) and HATU (5) exist in the N-form (guanidinium salt) instead of the O-form (uronium salt) and that the two forms can easily be distinguished by means of 13 C-NMR spectroscopy. The carbocationic carbon of the N-form appears at 151-152 ppm while that of the O-form appears at 161-162 ppm [29,30].…”

Section: Preparation Of Tombu and Combumentioning

confidence: 99%

TOMBU and COMBU as Novel Uronium-Type Peptide Coupling Reagents Derived from Oxyma-B

et al. 2014

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Abstract:Here we describe two novel uronium salts, TOMBU and COMBU, derived from the recently described Oxyma-B for use in peptide bond synthesis. These coupling reagents are more stable than COMU in DMF. Furthermore, using various peptide synthetic models in solution and solid-phase synthesis, we reveal that they show better performance than OPEN ACCESSMolecules 2014, 19 18954 HBTU in terms of preserving chiral integrity and coupling yields, but slightly worse performance than COMU.

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“…They crystallize as aminium salts, as the guanidinium N-oxide isomers. 57 In solution the two forms could co-exist, since either could react with a carboxyl group to give the activated ester intermediate. Figure 28).…”

Section: Aminium Saltsmentioning

confidence: 99%

Evolution of amide bond formation

Joullié¹,

Lassen²

2010

Arkivoc

161

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This paper is dedicated to Drs Bruce E. Maryanoff and Cynthia A. Maryanoff for their outstanding contribution to organic chemistry as industrial chemists AbstractThe presence of carboxamide groups is found in a large array of biologically important compounds. Peptides and proteins play an important role in modern biology. A key step in peptide production is the formation of the peptide bond, which involves amide bond formation. Chemical synthesis of large peptides by intermolecular coupling of smaller peptides using conventional peptide bond-forming techniques did not realize its potential advantages until recently. Using an approach based on highly specific and efficient chemical ligation of two peptide segments, the two subunits were ligated to form a new peptide bond. Native chemical ligation extended the concept by creating a native peptide bond and providing new approaches to protein engineering.

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Structural studies of reagents for peptide bond formation: Crystal and molecular structures of HBTU and HATU

Cited by 104 publications

References 16 publications

Coupling of iminodiacetic acid with amino acid derivatives in solution and solid phase

Coupling of iminodiacetic acid with amino acid derivatives in solution and solid phase

TOMBU and COMBU as Novel Uronium-Type Peptide Coupling Reagents Derived from Oxyma-B

Evolution of amide bond formation

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