Catalytic hydrogenolysis in liquid ammonia: stability and cleavage of some protecting groups used in peptide synthesis

Meienhofer, Johannes; Kuromizu, Kenji

doi:10.1016/s0040-4039(01)91878-7

Cited by 38 publications

(8 citation statements)

References 25 publications

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Section: Results and Discussionmentioning

confidence: 99%

“…The mass increment of 468 Da with the theoretical mass of the native peptide (1714 Da) confirms the presence of the BP moiety which conserved the Z protecting group on its thiazolidine ring. All attempts to remove this protecting group were unsuccessful leading to the unchanged Z-BP-YG peptide (TFA) or to complete degradation (HF, p-cresol; 43 or H 2 , Pd/C, NH 3liq 44 ). Considering the difficulties both to protect and to cleanly deprotect the thiazolidine secondary amine, this protection appeared to be unnecessary, hypothesizing that the congested thiazolidine amino group could be far less reactive than the primary amine of the lysine part in the amidation reaction.…”

Section: ■ Introductionmentioning

confidence: 99%

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Bioinspired Design and Oriented Synthesis of Immunogenic Site-Specifically Penicilloylated Peptides

et al. 2016

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β-Lactam antibiotics allergy is recognized as a public health concern. By covalently binding to serum proteins, penicillins are known to form immunogenic complexes. The latter are recognized and digested by antigen-presenting cells into drug-hapten peptides leading to the immunization of treated persons and IgE-mediated hypersensitivity reactions encompassing anaphylaxis. If type I allergic reactions to drugs are often unpredictable, they are known to be dependent on CD4 T-cells. This fundamental study revisits the chemical basis of the benzylpenicillin (BP) allergy with the aim of identifying immunologically relevant biomimetic benzylpenicilloylated peptides through the analysis of BP-conjugated human serum albumin (BP-HSA) profile and the evaluation of the naı̈ve CD4 T-cell responses to candidate BP-HSA-derived peptides. The chemical structures of BP-HSA bioconjugates synthesized in vitro at both physiological and basic pH were investigated by mass spectrometry. From the ten most representative lysine residues grafted by BP-hapten, HSA-bioinspired 15-mer peptide sequences were designed and the potential T-cell epitope profile of each peptide was predicted using two complementary in silico approaches, i.e., HLA class II binding prediction tools from the Immune Epitope Database and Analysis Resource (IEDB) and computational alanine scanning mutagenesis. Twelve structurally diversified benzylpenicilloylated peptides (BP-Ps) were selected and synthesized with the aid of a flexible synthesis pathway using an original benzylpenicilloylated lysine monomer as common precursor. In order to corroborate their predicted "epitope" profile, the naı̈ve CD4 T-cell response specific to BP was evaluated through a coculture approach. To our knowledge, this study showed for the first time the ability of bioinspired peptides structurally stemming from BP-HSA to be recognized by naı̈ve CD4 T-cells thus identifying a pre-existing T-cell repertoire for penicillin molecules bound to proteins. It also established a promising model approach expandable to other most frequently used penicillin classes of antibiotics to reveal biomimetic drug-modified antigenic peptides relevant for qualitative and quantitative drug allergy studies.

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Section: Results and Discussionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Bioinspired Design and Oriented Synthesis of Immunogenic Site-Specifically Penicilloylated Peptides

et al. 2016

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“…The products 30a − e were isolated as glassy solids, which on triturating with hexane gave the desired products as white solids in good to excellent yields (78−97%). Although the reaction was successful for the derivatives 29a − e , the N- cyclopropylthiocarbamoyl derivative 29f failed to undergo hydrogenolysis even in the presence of high percentage (50%) of the catalyst due to the presence of sulfur in 29f poisoning the catalyst . Finally, the protection of the α-amino function of compounds 30a − e with the Fmoc group was readily achieved by acylation with FmocOSu in the presence of NaHCO 3 in dioxane/water mixture affording compounds 31a − e in 51−88% yields.…”

Section: Resultsmentioning

confidence: 99%

Homochiral 4-Azalysine Building Blocks: Syntheses and Applications in Solid-Phase Chemistry¹

2002

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Anomalous amino acids not only play central roles as mimics of natural amino acids but also offer opportunities as unique building blocks for combinatorial chemistry. This paper describes the chiral syntheses and solid-phase applications of a versatile atypical amino acid, 4-azalysine (2,6-diamino-4-azahexanoic acid) 1. The syntheses of differentially protected 4-azalysine derivatives 28a-e have been developed by two efficient and inexpensive routes that start either from Garner's aldehyde 16 or the chiron (S)-N(alpha)-Cbz-2,3-diaminopropionic acid 23. Both approaches employ the convergent modular concept and exploit reductive amination of aldehydes with amines as the key step for the fusion of the two segments. In the first route, the overall process inverts the chirality of the starting material, L-serine, and thus provides an excellent route to the unnatural D-isomers. The alternative route starting from L-asparagine provides a shorter and high-yielding route to orthogonally protected 4-azalysine derivatives. The corresponding N(2)-Fmoc-4-azalysines 31a-e, readily derived from the key intermediate 27, are compatible with the Fmoc-based solid-phase peptide synthesis (SPPS) and solid-phase organic chemistry (SPOC) protocols. Furthermore, the utility and versatility of another key structure, tris-Boc-4-azalysine 2 in the engineering of novel high-loading dendrimeric polystyrene resins 33 and 36, have been demonstrated. Following derivatization with the Rink amide linker 34, the stability and robustness of these resin-bound dendrimers 35 and 37 in the synthesis of small molecules using a range of reaction conditions (e.g., Mitsunobu and Suzuki reactions) have been effectively illustrated.

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“…Benzyl esters of sulfur-containing 36j 1 Protection Reactions peptides can be cleaved without poisoning of the catalyst by carrying out catalytic hydrogenation in liquid NH 3 solvent at À33 C (boiling point of NH 3 ) for 16-18 h [163]. Benzyl esters are cleaved through CTH (e.g., Pd/C, 85% HCOOH) within minutes at 25 C [47].…”

Section: Cleavagementioning

confidence: 99%

Protection Reactions

Sureshbabu¹,

Narendra²

2011

Amino Acids, Peptides and Proteins in Organic Chemistry

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Catalytic hydrogenolysis in liquid ammonia: stability and cleavage of some protecting groups used in peptide synthesis

Cited by 38 publications

References 25 publications

Bioinspired Design and Oriented Synthesis of Immunogenic Site-Specifically Penicilloylated Peptides

Bioinspired Design and Oriented Synthesis of Immunogenic Site-Specifically Penicilloylated Peptides

Homochiral 4-Azalysine Building Blocks: Syntheses and Applications in Solid-Phase Chemistry¹

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Catalytic hydrogenolysis in liquid ammonia: stability and cleavage of some protecting groups used in peptide synthesis

Cited by 38 publications

References 25 publications

Bioinspired Design and Oriented Synthesis of Immunogenic Site-Specifically Penicilloylated Peptides

Bioinspired Design and Oriented Synthesis of Immunogenic Site-Specifically Penicilloylated Peptides

Homochiral 4-Azalysine Building Blocks: Syntheses and Applications in Solid-Phase Chemistry1

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Homochiral 4-Azalysine Building Blocks: Syntheses and Applications in Solid-Phase Chemistry¹