Fmoc-Compatible and C-terminal-Sequence-Independent Peptide Alkyl Thioester Formation Using Cysteinylprolyl Imide

Nakatsu, Koki; Yanase, Masafumi; Hayashi, Gosuke; Okamoto, Akimitsu

doi:10.1021/acs.orglett.0c01450

Cited by 7 publications

(3 citation statements)

References 42 publications

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“…We tested the compatibility of AMDBH with thioester moieties under standard NCL conditions (pH≈7). Glycyl thioester peptide 2 (H‐SYRKG‐diketopiperazine (DKP) thioester) was synthesized using an Fmoc‐compatible peptide thioesterification method based on cysteinyl prolyl imide (CPI), which we previously reported (Figure S10) [44, 45] . Peptide 2 was exposed to 200 mM methoxyamine or AMDBH in an NCL buffer at pH 7.0 or 7.5, and the reaction was monitored by RP‐HPLC and MALDI‐TOF‐MS (Figure 2a).…”

Section: Resultsmentioning

confidence: 99%

Repetitive Thiazolidine Deprotection Using a Thioester‐Compatible Aldehyde Scavenger for One‐Pot Multiple Peptide Ligation**

et al. 2022

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Strategies for one-pot peptide ligation enable chemists to access synthetic proteins at a high yield in a short time. Herein, we report a novel one-pot multisegments ligation strategy using N-terminal thiazolidine (Thz) peptide and a newly designed formaldehyde scavenger. Among the designed 2-aminobenzamidebased aldehyde scavengers, 2-amino-5-methoxy-N',N'dimethylbenzohydrazide (AMDBH) can remarkably convert Thz into unprotected cysteine at pH 4.0. Furthermore, AMDBH degrades Thz at a considerably low rate at pH 7.5, and thioester degradation caused by this scavenger is negligible. As a result, we have developed an efficient one-pot peptide ligation strategy by simply repetitively changing the pH with AMDBH. Finally, we synthesize mono-ubiquitinated histone H2A.Z (209 amino acids) via AMDBH-mediated one-pot four-segment peptide ligation in good yield.

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Section: Resultsmentioning

confidence: 99%

Repetitive Thiazolidine Deprotection Using a Thioester‐Compatible Aldehyde Scavenger for One‐Pot Multiple Peptide Ligation**

et al. 2022

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“…Glycyl thioester peptide 2 (H-SYRKG-diketopiperazine (DKP) thioester) was synthesized using an Fmoc-compatible peptide thioesterification method based on cysteinyl prolyl imide (CPI), which we previously reported (Figure S10). [44,45] Peptide 2 was exposed to 200 mM methoxyamine or AMDBH in an NCL buffer at pH 7.0 or 7.5, and the reaction was monitored by RP-HPLC and MALDI-TOF-MS (Figure 2a). For methoxyamine, the thioester peptide was quantitatively converted into C-terminal methoxyamine-adduct 2-MA within 1 h at pH 7.0 and 7.5 (Figures 2b and S11b).…”

Section: Methodsmentioning

confidence: 99%

Repetitive Thiazolidine Deprotection Using a Thioester‐Compatible Aldehyde Scavenger for One‐Pot Multiple Peptide Ligation**

et al. 2022

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Strategies for one‐pot peptide ligation enable chemists to access synthetic proteins at a high yield in a short time. Herein, we report a novel one‐pot multi‐segments ligation strategy using N‐terminal thiazolidine (Thz) peptide and a newly designed formaldehyde scavenger. Among the designed 2‐aminobenzamide‐based aldehyde scavengers, 2‐amino‐5‐methoxy‐N′,N′‐dimethylbenzohydrazide (AMDBH) can remarkably convert Thz into unprotected cysteine at pH 4.0. Furthermore, AMDBH degrades Thz at a considerably low rate at pH 7.5, and thioester degradation caused by this scavenger is negligible. As a result, we have developed an efficient one‐pot peptide ligation strategy by simply repetitively changing the pH with AMDBH. Finally, we synthesize mono‐ubiquitinated histone H2A.Z (209 amino acids) via AMDBH‐mediated one‐pot four‐segment peptide ligation in good yield.

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“…Glycyl thioester peptide 2 (H-SYRKG-diketopiperazine (DKP) thioester) was synthesized using an Fmoc-compatible peptide thioesterification method based on Cysteinyl Prolyl Imide (CPI), which we reported previously (Figure S10.). [43,44] The peptide 2 was exposed to 200 mM methoxyamine or AMDBH buffer based on 'condition A' at pH 7.0 or 7.5 and the reaction was monitored by RP-HPLC and MALDI-TOF/MS (Figure 2a.). In the case of methoxyamine, the thioester peptide was quantitatively converted into C-terminal methoxyamine adduct 2-MA within 1 h both at pH 7.0 and at 7.5 (Figure 2b and S11b).…”

Section: Compatibility Of Aldehyde Scavengers To a Thioester Moiety At Ncl Conditionsmentioning

confidence: 99%

Thiazolidine Deprotection by 2-Aminobenzamide-Based Aldehyde Scavenger for One-Pot Multiple Peptide Ligation

Nakatsu¹,

Murakami²,

Hayashi³

et al. 2021

Preprint

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Strategies for one-pot peptide ligation enable chemists to access synthetic proteins at a high yield in a short time. Herein, we report a new one-pot multi-segments ligation strategy using N-terminal thiazolidine (Thz) peptide and a formaldehyde scavenger. Among our designed 2-aminobenzamide-based aldehyde scavengers, 2-amino-5-methoxy-N’,N’-dimethylbenzohydrazide showed a good ability to capture formaldehyde from Thz at pH 4.0. This scavenger had compatibility with the conditions of native chemical ligation at pH 7.5. Using this scavenger for a model peptide ligation system, we performed one-pot four-segment ligation at a high yield without significant side reactions.

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Fmoc-Compatible and C-terminal-Sequence-Independent Peptide Alkyl Thioester Formation Using Cysteinylprolyl Imide

Cited by 7 publications

References 42 publications

Repetitive Thiazolidine Deprotection Using a Thioester‐Compatible Aldehyde Scavenger for One‐Pot Multiple Peptide Ligation**

Repetitive Thiazolidine Deprotection Using a Thioester‐Compatible Aldehyde Scavenger for One‐Pot Multiple Peptide Ligation**

Repetitive Thiazolidine Deprotection Using a Thioester‐Compatible Aldehyde Scavenger for One‐Pot Multiple Peptide Ligation**

Thiazolidine Deprotection by 2-Aminobenzamide-Based Aldehyde Scavenger for One-Pot Multiple Peptide Ligation

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