Facile hydrolysis and formation of amide bonds by N-hydroxyethylation of α-amino acids

Suggs, J. William; Pires, Richard M.

doi:10.1016/s0040-4039(97)00330-4

Cited by 18 publications

(15 citation statements)

References 14 publications

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“…PEG 95,96 fragment via formation of morpholinolactones 71 or 72 upon a single enzyme activation (Scheme 12). In line with the results reported earlier by Suggs, 97 following hydrolytic cleavage of the second PEG chain to form diol 73, an enhanced rate of cyclisation-elimination to afford 72, was observed. The reasons behind this rate enhancement are not completely clear.…”

Section: Peg Polymer Conjugatessupporting

confidence: 92%

Self-immolative linkers in polymeric delivery systems

et al. 2011

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There has been significant interest in the methodologies of controlled release for a diverse range of applications spanning drug delivery, biological and chemical sensors, and diagnostics. The advancement in novel substrate-polymer coupling moieties has led to the discovery of selfimmolative linkers. This new class of linker has gained popularity in recent years in polymeric release technology as a result of stable bond formation between protecting-and leaving groups, which becomes labile upon activation, leading to the rapid disassembly of the parent polymer. This ability has prompted numerous studies into the design and development of self-immolative linkers and the kinetics surrounding their disassembly. This review details the main concepts that underpin self-immolative linker technologies that feature in polymeric or dendritic conjugate systems and outlines the chemistries of amplified self-immolative elimination. 65 For the purpose of clarity, a colour scheme has been adopted to highlight trigger (blue), self-immolative linker (green) and reporter (red) moieties.

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Section: Peg Polymer Conjugatessupporting

confidence: 92%

Self-immolative linkers in polymeric delivery systems

et al. 2011

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“…For model peptide 11, use of the above conditions to remove the Hgm group requires three days to complete the reaction to give the target peptide in 91% yield. This observation is consistent with the previous findings by Suggs et al 16 and Hansen et al 17 shown in Figure 1. Thus, for practical purposes, the Hqm group is more useful.…”

supporting

confidence: 94%

“…Noting the difficulty of amide bond cleavage under mild conditions, we turn to the idea of using intramolecular acyl transfer to promote the deprotection reaction. Previous studies by the groups of Suggs and Hansen provide interesting examples for rapid cleavage of unactivated amide bonds at neutral pH (Figure ). Accordingly, we designed Hgm and Hqm groups (nomenclature for Hgm and Hqm is explained in the Supporting Information) for the protection of a thiol (Figure ), in which the OAc moiety is removed by aqueous hydrazine to trigger the deprotection event.…”

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confidence: 99%

Hydrazine-Sensitive Thiol Protecting Group for Peptide and Protein Chemistry

Shen

Zhang

et al. 2011

Org. Lett.

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In the search for a new Cys side-chain protecting group that is compatible to the solid-phase peptide synthesis yet can be removed under mild conditions, the Hqm and Hgm groups that are readily deprotected by using aqueous hydrazine have been developed. The utility of these groups for peptide and protein chemistry is tested by the total synthesis of a peptide antibiotic trifolitoxin and the human neutrophil defensin hNP2.

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“…In 1997, a report appeared by Suggs that described the rapid hydrolysis of C-terminal amides of glycine at 25 °C and pH 7 when the N -terminus is N -hydroxyethylated. The t 1/2 of bis -N -2-hydroxyethylglycinamide ( 1 ) in 0.1 M phosphate buffer was determined to be 3 h, which is exceptionally better than the 7 yr reported for the unsubstituted glycinamide .…”

Section: Introductionmentioning

confidence: 99%

A New Aliphatic Amino Prodrug System for the Delivery of Small Molecules and Proteins Utilizing Novel PEG Derivatives

et al. 2003

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A new amino PEG prodrug system, based entirely on aliphatic structures, has been designed using ester derivatives easily synthesized from N-modified bis-N-2-hydroxyethylglycinamides. Hydrolysis of the various promoiety bonds, in vivo, regenerated amine in a predictable manner. Thus, a novel new methodology for controlled release of amino-containing drugs, peptides, and proteins has been accomplished. This work demonstrates the usefulness of a PEG prodrug strategy that results in solubilization of insoluble amino-containing drugs and provides prodrugs with relatively long circulating half-lives. It can be appreciated that this novel system should also be applicable for nonpolymer-containing prodrugs as well.

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Facile hydrolysis and formation of amide bonds by N-hydroxyethylation of α-amino acids

Cited by 18 publications

References 14 publications

Self-immolative linkers in polymeric delivery systems

Self-immolative linkers in polymeric delivery systems

Hydrazine-Sensitive Thiol Protecting Group for Peptide and Protein Chemistry

A New Aliphatic Amino Prodrug System for the Delivery of Small Molecules and Proteins Utilizing Novel PEG Derivatives

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