A new method for the solid phase synthesis of hydroxyethylamine peptide bond isosteres : Synthesis of an HIV-1 protease inhibitor and of a β-casomorphin-5 analogue.

Tourwé, Dirk; Piron, J.; Defreyn, P.; Binst, G. Van

doi:10.1016/s0040-4039(00)73945-1

Cited by 15 publications

(3 citation statements)

References 12 publications

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“…On the other hand, less reactive alkyl halides, such as homopropargyl tosylate, did not react at all. Accordingly, we turned our attention to a reductive alkylation approach, which has been used with considerable success on the solid phase, − including for the synthesis of aegPNA . It was, however, unknown from the literature whether the reductive alkylation will be compatible with the unprotected amino groups of the nucleobases C, A, and G. A model reductive alkylation reaction was, therefore, performed on a short APC-modified acpcPNA tetramer (G CT A) in the presence of butyraldehyde (30 equiv), NaBH 3 CN (60 equiv), and HOAc (60 equiv) in methanol.…”

Section: Resultsmentioning

confidence: 99%

Reductive Alkylation and Sequential Reductive Alkylation-Click Chemistry for On-Solid-Support Modification of Pyrrolidinyl Peptide Nucleic Acid

et al. 2013

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A methodology for the site-specific attachment of fluorophores to the backbone of pyrrolidinyl peptide nucleic acids (PNAs) with an α/β-backbone derived from D-prolyl-(1S,2S)-2-aminocyclopentanecarboxylic acid (acpcPNA) has been developed. The strategy involves a postsynthetic reductive alkylation of the aldehyde-containing labels onto the acpcPNA that was previously modified with (3R,4S)-3-aminopyrrolidine-4-carboxylic acid on the solid support. The reductive alkylation reaction is remarkably efficient and compatible with a range of reactive functional groups including Fmoc-protected amino, azide, and alkynes. This allows further attachment of readily accessible carboxyl-, alkyne-, or azide-containing labels via amide bond formation or Cu-catalyzed azide-alkyne cycloaddition (CuAAC, also known as click chemistry). The label attached in this way does not negatively affect the affinity and specificity of the pairing of the acpcPNA to its DNA target. Applications of this methodology in creating self-reporting pyrene- and thiazole orange-labeled acpcPNA probes that can yield a change in fluorescence in response to the presence of the correct DNA target have also been explored. A strong fluorescence enhancement was observed with thiazole orange-labeled acpcPNA in the presence of DNA. The specificity could be further improved by enzymatic digestion with S1 nuclease, providing a 9- to 60-fold fluorescence enhancement with fully complementary DNA and a less than 3.5-fold enhancement with mismatched DNA targets.

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Section: Resultsmentioning

confidence: 99%

Reductive Alkylation and Sequential Reductive Alkylation-Click Chemistry for On-Solid-Support Modification of Pyrrolidinyl Peptide Nucleic Acid

et al. 2013

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“…Scheme 106 depicts several aldehydes and the diastereomeric ratio obtained for recent examples which utilized 2-TST. [197][198][199][200][201][202][203] Dondoni has also demonstrated the use of 2-TST for the addition to fluorinated aryl and alkyl ketones (Scheme 107). 204 Acetophenones and other ketones have not been successful as electrophiles for 2-TST.…”

Section: -Trimethylsilyl Azolesmentioning

confidence: 99%

Current methods for the synthesis of 2-substituted azoles

2004

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“…We therefore developed a new method that is compatible with Solid Phase Peptide Synthesis and where the HEA isostere is formed by reductive amination of an c~-hydroxyaldehyde [8]. This c~-hydroxyaldehyde can be converted into the ~-hydroxyacid, which can be incorporated in a peptide to form the hydroxymethylamide (HMA) isostere (Scheme 2).…”

Section: Introductionmentioning

confidence: 99%

New methods for solid phase peptide synthesis of transitionstate analog inhibitors of HIV-1 protease and DPP-IV

Piron¹,

Tourwé²

1995

Lett Pept Sci

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A new and stereoselective method to synthesize hydroxyethylamine and hydroxymethylamide peptide bond isosteres is developed. The key step is the addition of 2-trimethylsilylthiazole to cc-aminoaldehydes, followed by transformation to c~-hydroxy-l]-aminoaldehydes. The stereochemistry of the addition can be manipulated by the choice of the nitrogen substitution. The isosteres are easily synthesized via Solid Phase Peptide Synthesis, which rapidly gives the desired pseudopeptides.

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A new method for the solid phase synthesis of hydroxyethylamine peptide bond isosteres : Synthesis of an HIV-1 protease inhibitor and of a β-casomorphin-5 analogue.

Cited by 15 publications

References 12 publications

Reductive Alkylation and Sequential Reductive Alkylation-Click Chemistry for On-Solid-Support Modification of Pyrrolidinyl Peptide Nucleic Acid

Reductive Alkylation and Sequential Reductive Alkylation-Click Chemistry for On-Solid-Support Modification of Pyrrolidinyl Peptide Nucleic Acid

Current methods for the synthesis of 2-substituted azoles

New methods for solid phase peptide synthesis of transitionstate analog inhibitors of HIV-1 protease and DPP-IV

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