Incorporation of 2-hydroxy-4-methoxybenzyl protection during peptide synthesis via reductive alkylation on the solid phase

Ede, Nicholas J.; Ang, K. H.; James, Ian W.; Bray, Andrew M.

doi:10.1016/s0040-4039(96)02095-3

Cited by 19 publications

(13 citation statements)

References 13 publications

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“…Imine formation was achieved with the addition of a slight excess of 2‐hydroxy‐4‐methoxy‐5‐nitrobenzaldehyde onto peptidyl‐resin 1 . Like most salicyaldehydes, 2‐hydroxy‐4‐methoxy‐5‐nitrobenzaldehyde forms exceptionally stable imines . Furthermore, the imine 2 was smoothly reduced to secondary amine using 5 equivalents of sodium borohydride.…”

Section: Resultsmentioning

confidence: 99%

A backbone amide protecting group for overcoming difficult sequences and suppressing aspartimide formation

Abdel–Aal

Papageorgiou

Raz

et al. 2016

Journal of Peptide Science

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A backbone amide bond protecting group, 2‐hydroxy‐4‐methoxy‐5‐nitrobenzyl (Hmnb), improved the synthesis of aggregation and aspartimide‐prone peptides. Introduction of Hmnb is automated and carried out during peptide assembly by addition of 4‐methoxy‐5‐nitrosalicylaldehyde to the peptidyl‐resin and on‐resin reduction to the secondary amine. Acylation of the hindered secondary amine is aided by the formation of an internal nitrophenol ester that undergoes a favourable O,N intramolecular acyl transfer. This activated ester participates in the coupling and generally gives complete reaction with standard coupling conditions. Hmnb is easily available in a single preparative step from commercially available material. Different methods for removing the amide protecting group were explored. The protecting group is labile to acidolysis, following reduction of the nitro group to the aniline. The two main uses of backbone protection of preventing aspartimide formation and of overcoming difficult sequences are demonstrated, first with the synthesis of a challenging aspartimide‐prone test sequence and then with the classic difficult sequence ACP (65‐74) and a 23‐mer homopolymer of polyalanine.

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Section: Resultsmentioning

confidence: 99%

A backbone amide protecting group for overcoming difficult sequences and suppressing aspartimide formation

Abdel–Aal

Papageorgiou

Raz

et al. 2016

Journal of Peptide Science

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“…We tried both approaches, with and without AcHmb-protection, in practical glycopeptide synthesis. The N-AcHmb protection of the Ala residue was on-resin, incorporated using published procedures (Ede et al, 1996). Both approaches gave the desired glycopeptide Glyco-MART-1 with good yield, but with AcHmb-protection, the crude product was better quality and did not contain the aspartimide by-product.…”

Section: Preparation Of Synthetic Peptidesmentioning

confidence: 99%

Terminal modifications inhibit proteolytic degradation of an immunogenic mart-127-35 peptide: Implications for peptide vaccines

et al. 1999

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“…An important advance was the demonstration of on‐resin reduction of Hmb onto the peptide resin . The reductive amination was quantitative with a single equivalent of the salicylaldehyde precursor.…”

Section: Introductionmentioning

confidence: 99%

Advances in Fmoc solid‐phase peptide synthesis

Behrendt

White

Offer

2016

Journal of Peptide Science

562

426

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Today, Fmoc SPPS is the method of choice for peptide synthesis. Very‐high‐quality Fmoc building blocks are available at low cost because of the economies of scale arising from current multiton production of therapeutic peptides by Fmoc SPPS. Many modified derivatives are commercially available as Fmoc building blocks, making synthetic access to a broad range of peptide derivatives straightforward. The number of synthetic peptides entering clinical trials has grown continuously over the last decade, and recent advances in the Fmoc SPPS technology are a response to the growing demand from medicinal chemistry and pharmacology. Improvements are being continually reported for peptide quality, synthesis time and novel synthetic targets. Topical peptide research has contributed to a continuous improvement and expansion of Fmoc SPPS applications. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

show abstract

Incorporation of 2-hydroxy-4-methoxybenzyl protection during peptide synthesis via reductive alkylation on the solid phase

Cited by 19 publications

References 13 publications

A backbone amide protecting group for overcoming difficult sequences and suppressing aspartimide formation

A backbone amide protecting group for overcoming difficult sequences and suppressing aspartimide formation

Terminal modifications inhibit proteolytic degradation of an immunogenic mart-127-35 peptide: Implications for peptide vaccines

Advances in Fmoc solid‐phase peptide synthesis

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