Solid phase synthesis of C-terminal carbohydrate modified enkephalins

Drouillat, Bruno; Kellam, Barrie; Dékány, Gyula; Starr, Mike S.; Tóth, István

doi:10.1016/s0960-894x(97)00395-8

Cited by 36 publications

(31 citation statements)

References 22 publications

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“…More significantly however, the C-terminus conjugation of one or two glucuronic acid units to the peptide led to a dramatic increase in activity -of up to 40-fold -in these assays with improved -opioid receptor selectivity [7,8]. We have also showed that these glucose and lipid modified enkephalin analogues show greatly enhanced permeability across the Caco-2 cell monolayer in in vitro assays of absorption [9].…”

Section: Introductionmentioning

confidence: 75%

Investigation of the Route of Absorption of Lipid and Sugar Modified Leu- Enkephalin Analogues and Their Enzymatic Stability Using the Caco-2 Cell Monolayer System

Wu¹,

Campbell²,

Koda³

et al. 2006

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It has been demonstrated that conjugation of lipoamino acids or glucose units to the endogenous opioid peptide, Leu-enkephalin can significantly improve the peptide's metabolic stability and absorption across biological barriers. The purpose of this study was to investigate the possible involvement of specific carrier proteins in the absorption of these peptide conjugates. A series of lipo- glycol- and liposaccharide peptide conjugates were synthesised and examined using the Caco-2 monolayer assay for evidence of interaction with the human H(+)-coupled oligopeptide transporter (hPepT1), glucose transporters and the multidrug resistance efflux pump, p-glycoprotein. The investigation involved determining the apparent permeability of each compound in the absence of any inhibitors and comparing this to the apparent permeabilities of each compound in the presence of glycylsarcosine, glucose or vinblastine, respective inhibitors of the above mentioned transporters. None of the peptide conjugates were found to be substrates for p-glycoprotein. Of the six peptide conjugates examined, only the C-terminus glucose conjugate of Leu-enkephalin (Enk-glu) showed evidence of transport by both glucose transporters and hPepT1. In contrast, N-terminus conjugation of both lipids and sugars appeared to provide the greatest protection against enzymatic degradation.

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Section: Introductionmentioning

confidence: 75%

Investigation of the Route of Absorption of Lipid and Sugar Modified Leu- Enkephalin Analogues and Their Enzymatic Stability Using the Caco-2 Cell Monolayer System

Wu¹,

Campbell²,

Koda³

et al. 2006

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“…14,18,19 The glycosyl azides 1a-g were synthesized according to known procedures. [20][21][22][23][24][25][26][27] The glycosyl units 2a-h were obtained by the acylation and in situ hydrogenation 28 of 1a-h (Scheme 1).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of glycolipopeptidic building blocks for carbohydrate receptor discovery

Ziora

Wimmer

New

et al. 2011

Carbohydrate Research

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“…54,55 Such sequences prepared by Chakraborty et al 56,57 have shown analgesic activity similar to that of Leuenkephalin methyl ester. Similarly, Drouillat et al 58 has used SAAs to form glycosylated enkephalins via amide bond linkages to the C-terminal. A 1-azido glucuronic acid was anchored to a trityl resin through the carboxylic acid, after which the amine functionality was formed by on-resin reduction with propane-1,3-dithiol.…”

Section: Figurementioning

confidence: 99%

Carbohydrates in peptide and protein design

Jensen¹,

Brask²

2005

Biopolymers

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Monosaccharides and amino acids are fundamental building blocks in the assembly of nature's polymers. They have different structural aspects and, to a significant extent, different functional groups. Oligomerization gives rise to oligosaccharides and peptides, respectively. While carbohydrates and peptides can be found conjoined in nature, e.g., in glycopeptides, the aim of this review is the radical redesign of peptide structures using carbohydrates, particularly monosaccharides and cyclic oligosaccharides, to produce novel peptides, peptidomimetics, and abiotic proteins. These hybrid molecules, chimeras, have properties arising largely from the combination of structural characteristics of carbohydrates with the functional group diversity of peptides. This field includes de novo designed synthetic glycopeptides, sugar (carbohydrate) amino acids, carbohydrate scaffolds for nonpeptidal peptidomimetics of cyclic peptides, cyclodextrin functionalized peptides, and carboproteins, i.e., carbohydrate-based proteinmimetics. These successful applications demonstrate the general utility of carbohydrates in peptide and protein architecture. #

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Solid phase synthesis of C-terminal carbohydrate modified enkephalins

Cited by 36 publications

References 22 publications

Investigation of the Route of Absorption of Lipid and Sugar Modified Leu- Enkephalin Analogues and Their Enzymatic Stability Using the Caco-2 Cell Monolayer System

Investigation of the Route of Absorption of Lipid and Sugar Modified Leu- Enkephalin Analogues and Their Enzymatic Stability Using the Caco-2 Cell Monolayer System

Synthesis of glycolipopeptidic building blocks for carbohydrate receptor discovery

Carbohydrates in peptide and protein design

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