A highly efficient in situ N-acetylation approach for solid phase synthesis

Chandra, Koushik; Roy, Tapta Kanchan; Naoum, Johnny N.; Gilon, Chaim; Gerber, R. Benny; Friedler, Assaf

doi:10.1039/c3ob42096e

Cited by 13 publications

(10 citation statements)

References 43 publications

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“…Using solid‐phase peptide synthesis (SPPS), we synthesized the peptide Su‐W‐LEDGF 361–370 (K Ac ) ((Su‐WNSLK(Ac)IDNLDV‐NH 2 ) 1 , Scheme ) by coupling succinic acid in the presence of a coupling reagent (HATU) and a base (DIPEA) to the Rink amide bound LEDGF 361–370 bearing an acetylated lysine (Scheme ) . The completion of the succinic acid coupling was confirmed by negative response to Kaiser‐ninhydrin and chloranil tests .…”

Section: Resultsmentioning

confidence: 99%

Covalent Inhibition of HIV‐1 Integrase by N‐Succinimidyl Peptides

et al. 2016

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We present a new approach for the covalent inhibition of HIV-1 integrase (IN) by an LEDGF/p75-derived peptide modified with an N-terminal succinimide group. The covalent inhibition is mediated by direct binding of the succinimide to the amine group of a lysine residue in IN. The peptide serves as a specific recognition sequence for the target protein, while the succinimide serves as the binding moiety. The combination of a readily synthesizable peptide precursor with easy and efficient binding to the target protein makes this approach a promising new strategy for designing lead compounds.

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Section: Resultsmentioning

confidence: 99%

Covalent Inhibition of HIV‐1 Integrase by N‐Succinimidyl Peptides

et al. 2016

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“…Prior to the evaluation of the purification linkers, we surveyed the literature with the aim to obtain information about the most effective capping protocols. Surprisingly, we identified only one report describing capping yields . Owing to the lack of published data, we examined an array of rapid capping conditions (Table S1, S2).…”

Section: Resultsmentioning

confidence: 99%

“…Immobilization of aminooxy and hydrazine linker modified peptides ( L1Me/L2 )‐AKADEVSLHKWYG‐OH on aldehyde modified agarose beads at pH 4.5 in 0.2 M sodium citrate. (A) Immobilization with and without oxime/hydrazone‐ligation catalysts (aniline, 3,5‐diaminobenzoic acid (DABA)) on 17 eq aldehyde agarose beads. (B) Percentage of oxime anchored peptide L1Me ‐AKADEVSLHKWYG‐OH over time in dependence of the equivalents of aldehyde groups on purification resin…”

Section: Resultsmentioning

confidence: 99%

A traceless catch‐and‐release method for rapid peptide purification

Reimann

Seitz

Sarma

et al. 2018

Journal of Peptide Science

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In contrast to peptide synthesis, peptide purification by high performance liquid chromatography (HPLC) cannot be easily varied in number and scale, which results in production restraints. Catch-and-release purification of peptides may help to ease HPLCrelated limitations and provides thus an alternative, allowing for fast protocols with great potential for parallelization and scale-up. This work depicts a unique combination of base-labile cleavable linkers with oxime-based and hydrazone-based ligation chemistry. For the first time, aminooxy or hydrazine functionalities are presented on site of the linker molecules. Aldehyde-functionalized agarose beads are used for immobilization on the solid phase, allowing a rapid and high yielding purification protocol. In this experimental set-up, many organic solvents or chaotropic reagents are accepted during immobilization, facilitating the dissolution of potentially hydrophobic or aggregation-prone peptides. Feasibility of the system is demonstrated with six peptides ranging from 15 to 31 residues in length, including very hydrophobic and thus challenging sequences like the palmitoyl modified liraglutide and an aggregation prone beta-amyloid fragment. Additionally, limitations of this system and the use of baselabile linkers are discussed and demonstrated.

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“…Peptides derived from binding interfaces may bind weaker than the parent protein, partly due to loss of secondary structure. Modifications such as post-translational modifications (e.g., acetylation or phosphorylation) [58,59], labeling (e.g., fluorescein or biotin) or incorporation of nonnatural amino acids can be inserted specifically into a protein sequence only using chemical peptide synthesis [60,61]. Peptides are an excellent model for binding studies of protein domains.…”

Section: Peptides As a Tool To Study Ppimentioning

confidence: 99%

Interactions of HIV-1 Proteins as Targets for Developing Anti-HIV-1 Peptides

2015

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Protein-protein interactions (PPI) are essential in every step of the HIV replication cycle. Mapping the interactions between viral and host proteins is a fundamental target for the design and development of new therapeutics. In this review, we focus on rational development of anti-HIV-1 peptides based on mapping viral-host and viral-viral protein interactions all across the HIV-1 replication cycle. We also discuss the mechanism of action, specificity and stability of these peptides, which are designed to inhibit PPI. Some of these peptides are excellent tools to study the mechanisms of PPI in HIV-1 replication cycle and for the development of anti-HIV-1 drug leads that modulate PPI.

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A highly efficient in situ N-acetylation approach for solid phase synthesis

Cited by 13 publications

References 43 publications

Covalent Inhibition of HIV‐1 Integrase by N‐Succinimidyl Peptides

Covalent Inhibition of HIV‐1 Integrase by N‐Succinimidyl Peptides

A traceless catch‐and‐release method for rapid peptide purification

Interactions of HIV-1 Proteins as Targets for Developing Anti-HIV-1 Peptides

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