Chemoselective Alkylation of<i>N</i>-Alkylaminooxy-Containing Peptides

Carrasco, Michael R.; Silva, Oscar; Rawls, Katherine A.; Sweeney, Marisol S.; Lombardo, Adria A.

doi:10.1021/ol061289d

Cited by 6 publications

(6 citation statements)

References 10 publications

(6 reference statements)

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“…(Fig. 1, bottom) [21,31,32]. To corroborate this point, both GlcNAc-peptide 2 and GlcNAc-N[Me]-O-peptide 2 were peracetylated and analyzed by MALDI-TOF MS.…”

Section: Resultsmentioning

confidence: 76%

Neo-glycopeptides: the importance of sugar core conformation in oxime-linked glycoprobes for interaction studies

et al. 2008

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Carbohydrate binding proteins, such as lectins, are crucial in numerous biological recognition processes. While binding may be mediated by a single monosaccharide, several lectins have shown exquisite epimer and linkage recognition indicating that a larger structure is essential for optimal interaction. Several approaches have been described for their detailed study, including lectinosorbent assays, microarrays and surface plasmon resonance (SPR). Most of these approaches ignore that the aglycon-bound monosaccharide is often in a non-natural conformation that affects the occurring binding event. In this paper we demonstrate that oxime-bound glycans, employed in such approaches, occur predominantly in the open form (approximately 70%). Through the use of a secondary amine, the aglycon-bound monosaccharide in the resulting neo-glycopeptide probe is forced into the ring-form. Resulting structures were analyzed by means of nuclear magnetic resonance and differential derivatization experiments. The impact of ring closure was further demonstrated through interaction studies using SPR and various lectins with distinct binding specificities.

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“…(Fig. 1, bottom) [21,31,32]. To corroborate this point, both GlcNAc-peptide 2 and GlcNAc-N[Me]-O-peptide 2 were peracetylated and analyzed by MALDI-TOF MS.…”

Section: Resultsmentioning

confidence: 76%

Neo-glycopeptides: the importance of sugar core conformation in oxime-linked glycoprobes for interaction studies

et al. 2008

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“…Therefore, a method to realize site‐specific modification after the chemical synthesis and folding is desirable. Along this line, the chemoselectivity of the N ‐alkylaminooxy group with electrophiles, such as succinimidyl ester, activated haloalkanes, has been examined . In addition, N ‐alkylaminooxy groups have been extensively studied for the chemoselective glycosylation to create glycoconjugates and glycopeptides .…”

Section: Introductionmentioning

confidence: 99%

Site-specific labeling of synthetic peptide using the chemoselective reaction betweenN-methoxyamino acid and isothiocyanate

et al. 2015

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Site-specific labeling of synthetic peptides carrying N-methoxyglycine (MeOGly) by isothiocyanate is demonstrated. A nonapeptide having MeOGly at its N-terminus was synthesized by the solid-phase method and reacted with phenylisothiocyanate under various conditions. In acidic solution, the reaction specifically gave a peptide having phenylthiourea structure at its N-terminus, leaving side chain amino group intact. The synthetic human β-defensin-2 carrying MeOGly at its N-terminus or the side chain amino group of Lys(10) reacted with phenylisothiocyanate or fluorescein isothiocyanate also at the N-methoxyamino group under the same conditions, demonstrating that this method is generally useful for the site-specific labeling of linear synthetic peptides as well as disulfide-containing peptides.

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“…The Nmethylaminooxy nitrogen can also be selectively reacted with active esters at slightly acidic pH in the presence of competing nucleophiles such as the thiol group of cysteine or amino group of lysine (15). Peptides containing N-methylaminooxy amino acids have been chemoselectively alkylated with allylic, benzylic, and R-haloacetyl, N-ethylmaleimide, and hexyl acrylate groups in mildly acidic aqueous/organic solutions (14,16). It was therefore postulated that an 18 F-labeled N-methylaminooxy prosthetic group could provide a useful addition to the toolbox of PET labeling strategies.…”

Section: Introductionmentioning

confidence: 99%

A Novel Prosthetic Group for Site-Selective Labeling of Peptides for Positron Emission Tomography

et al. 2008

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Efficient methodologies for the radiolabeling of peptides with [(18)F]fluoride are a prerequisite to enabling commercialization of peptide-containing radiotracers for positron emission tomography (PET) imaging. It was the purpose of this study to investigate a novel chemoselective ligation reaction comprising conjugation of an [(18)F]-N-methylaminooxy-containing prosthetic group to a functionalized peptide. Twelve derivatives of general formula R1-CO-NH-Lys-Gly-Phe-Gly-Lys-OH were synthesized where R1 was selected from a short list of moieties anticipated to be reactive toward the N-methylaminooxy group. Conjugation reactions were initially carried out with nonradioactive precursors to assess, in a qualitative manner, their general suitability for PET chemistry with only the most promising pairings progressing to full radiochemical assessment. Best results were obtained for the ligation of O-[2-(2-[(18)F]fluoroethoxy)ethyl]-N-methyl-N-hydroxylamine 18 to the maleimidopropionyl-Lys-Gly-Phe-Gly-Lys-OH precursor 10 in acetate buffer (pH 5) after 1 h at 70 degrees C. The non-decay-corrected isolated yield was calculated to be 8.5%. The most encouraging result was observed with the combination 18 and 4-(2-nitrovinyl)benzoyl-Lys-Gly-Phe-Gly-Lys-OH, 9, where the conjugation reaction proceeded rapidly to completion at 30 degrees C after only 5 min. The corresponding non-decay-corrected radiochemical yield for the isolated (18)F-labeled product 27 was 12%. The preliminary results from this study demonstrate the considerable potential of this novel strategy for the radiolabeling of peptides.

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Chemoselective Alkylation ofN-Alkylaminooxy-Containing Peptides

Cited by 6 publications

References 10 publications

Neo-glycopeptides: the importance of sugar core conformation in oxime-linked glycoprobes for interaction studies

Neo-glycopeptides: the importance of sugar core conformation in oxime-linked glycoprobes for interaction studies

Site-specific labeling of synthetic peptide using the chemoselective reaction betweenN-methoxyamino acid and isothiocyanate

A Novel Prosthetic Group for Site-Selective Labeling of Peptides for Positron Emission Tomography

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