Dramatically enhanced N→O acyl migration during the trifluoroacetic acid-based deprotection step in solid phase peptide synthesis

Carpino, Louis A.; Krause, Eberhard; Sferdean, Calin Dan; Bienert, Michael; Beyermann, Michael

doi:10.1016/j.tetlet.2004.12.089

Cited by 22 publications

(19 citation statements)

References 18 publications

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“…Since no amino acid located outside the C 46 TKCGH 51 loop interacts with the ZnA C H T U N G T R E N N U N G (Cys) 4 core in the structure of RPB9, an 8 amino acid cycle (cyclo(PCKKCGW D P)) was chosen to mimic this loop. [67] This treatment should not exceed 1.5 h to reduce the amount of O-acetylated byproduct. In RPB9, the side chain of Thr47 points roughly in the direction of the Asn23 residue of the other loop and the distance between Thr47 Cb and Asn23 CO is approximately 7.5 (Figure 1 B).…”

Section: Resultsmentioning

confidence: 99%

On the Design of Zinc‐Finger Models with Cyclic Peptides Bearing a Linear Tail

Jacques

Mettra

Lebrun

et al. 2013

Chemistry A European J

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Cyclic peptides with a linear tail (CPLT) have been successfully used to model two zinc fingers (ZFs) adopting the treble-clef- and loosened zinc-ribbon folds. In this article, we examine the factors that may influence the design of such ZF models: mutations in the sequence, size of the cycle, and size of the tail. For this purpose, several peptides derived from the CPLT-based models of the treble-clef- and loosened zinc-ribbon ZF were synthesized and studied. CPLT-based models appear to be robust toward mutations, accommodate various cycle sizes, and are sensible to the size of the linking region of the tail located between the cycle and the coordinating amino acids. Based on these criteria, we describe the design of a new CPLT-based model for the zinc-ribbon ZFs, LZR , and compare it to a linear analogue, LZR(lin) . The model complex Zn⋅LZR is able to fold correctly around the metal ion contrary to Zn⋅LZR(lin) , suggesting that CPLT-based models are more likely to yield structurally meaningful models of ZF sites than linear peptide models. Finally, we draw some rules that could allow the design of new CPLT-based metallopeptides with a controlled fold.

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Section: Resultsmentioning

confidence: 99%

On the Design of Zinc‐Finger Models with Cyclic Peptides Bearing a Linear Tail

Jacques

Mettra

Lebrun

et al. 2013

Chemistry A European J

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“…The NO acyl migration of β‐amino alcohols, firstly described by Bergmann,1 is a well‐known side reaction in peptide synthesis 2. This reversible, pH‐dependent migration occurs in peptides or proteins at serine or threonine residues upon treatment with strong acid, but also in moderately acidic medium 3. It has been reported that strong acid treatment of polyserine amide promotes, as a side reaction, a partial NO acyl shift to produce an amide‐ester copolymer 4.…”

Section: Introductionmentioning

confidence: 99%

From Polyesters to Polyamides Via ON Acyl Migration: An Original Multi‐Transfer Reaction

Tailhades

Blanquer

Nottelet

et al. 2011

Macromol. Rapid Commun.

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A new strategy for the synthesis of polyamides from polyesters of hydroxyl-containing amino acids using a multi O-N acyl transfer reaction was developed. This original approach allowed the synthesis of three generations of polymers from the same starting monomer. The polymerization of N-benzyloxycarbonyl-serine and its γ-homologated derivative provided the Z-protected polyesters; then the water-soluble polycationic polyesters were obtained by removal of the Z-protecting group; and finally the polyamides were obtained by a base-induced multi O-N acyl transfer, both in aqueous or organic medium. The key step transfer reaction was monitored by the disappearance and appearance of characteristic NMR proton signals and IR bands of polyesters and polyamides.

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“…It has been described that this side-reaction can also be catalyzed by TFA during the cleavage/deprotection step ( Figure 10.12) [62]. O acyl migration in Ser-and Thr-containing peptides is known to occur upon exposure to strong acids such as HF used in the Boc/Bzl-based cleavage/deprotection step.…”

Section: Ser and Thr N ! O Migrationmentioning

confidence: 99%

Fmoc Methodology: Cleavage from the Resin and Final Deprotection

Alberício

Tulla‐Puche

Kates³

2010

Amino Acids, Peptides and Proteins in Organic Chemistry

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The fluorenylmethoxycarbonyl (Fmoc)/tert-butyl (tBu) solid-phase method is categorically the present strategy of choice for the preparation of peptides for both research and industrial scales [1][2][3][4][5]. The main advantage of the Fmoc/tBu approach compared to the earlier tert-butyloxycarbonyl (Boc)/benzyl (Bzl) strategy is the conditions used to remove the temporal protecting group (Fmoc) and the permanent side-chain protecting groups as well as the separation/cleavage of the peptide from the resin. For the Boc/Bzl strategy, each removal of the temporal protecting group (Boc) requires treatment with trifluoroacetic acid (TFA) and the final stepthe cleavage of the peptide from the resinideally requires the concourse of HF. Although HF provokes very clean chemical reactions and is an optimal reagent to incorporate into a synthetic strategy, its use requires special Teflon reservoirs and may be forbidden in some geographical areas by local safety departments. These drawbacks are further magnified at an industrial scale. Conversely, the Fmoc/tBu strategy requires typically one or a maximum of two acid treatments.The absence of TFA for the release of the temporal protecting group in the Fmoc/ tBu strategy allows a gradual removal/cleavage of the remaining protecting groups. A final treatment of the peptide resin with a high concentration of TFA (approximately 90%) will render the totally free unprotected peptide. Alternatively, after choosing the proper resin, it is possible first to remove the protected peptide from the resin (1-5% TFA) and then to obtain the free peptide by treatment with a high concentration of TFA (Figure 10.1). This two-step cleavage/deprotection strategy allows modulation of the TFA treatment to minimize side-reactions and therefore increase the quality of the final product.Conversely, the protected peptide may be further elongated in solution by reaction with other protected peptides also prepared by solid-phase to accomplish the target molecule (convergent strategy, Figure 10.2) [6,7].Although there has been continuous development of new resins, linkers, protecting groups, and coupling reagents (see Chapter 12), the treatment of the protected peptide(-resin) with a high concentration of TFA is perhaps the key step for obtaining

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Dramatically enhanced N→O acyl migration during the trifluoroacetic acid-based deprotection step in solid phase peptide synthesis

Cited by 22 publications

References 18 publications

On the Design of Zinc‐Finger Models with Cyclic Peptides Bearing a Linear Tail

On the Design of Zinc‐Finger Models with Cyclic Peptides Bearing a Linear Tail

From Polyesters to Polyamides Via ON Acyl Migration: An Original Multi‐Transfer Reaction

Fmoc Methodology: Cleavage from the Resin and Final Deprotection

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