Side-chain assisted ligation in protein synthesis

Kumar, K. S. Ajish; Harpaz, Ziv; Haj‐Yahya, Mahmood; Brik, Ashraf

doi:10.1016/j.bmcl.2009.03.156

Cited by 19 publications

(5 citation statements)

References 35 publications

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“…Although the ligations which could generate Ser/Thr at the ligation site have been developed by different groups (Okamoto and Kajihara, 2008; Ajish Kumar et al, 2009b; Thomas and Payne, 2009; Chen et al, 2010), our ligation strategy directly uses the natural serine or threonine residue at the N-terminus to mediate peptide ligation. This ligation strategy involves the merger of a peptide salicylaldehyde (SAL) ester and a peptide with N-terminal serine or threonine, to afford an N,O -benzylidene acetal at the conjugation site, followed by simple acidolysis to release the natural peptidic bond.…”

Section: Introductionmentioning

confidence: 99%

Realizing serine/threonine ligation: scope and limitations and mechanistic implication thereof

Wong

Lam

et al. 2014

Front. Chem.

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Serine/Threonine ligation (STL) has emerged as an alternative tool for protein chemical synthesis, bioconjugations as well as macrocyclization of peptides of various sizes. Owning to the high abundance of Ser/Thr residues in natural peptides and proteins, STL is expected to find a wide range of applications in chemical biology research. Herein, we have fully investigated the compatibility of the STL strategy for X-Ser/Thr ligation sites, where X is any of the 20 naturally occurring amino acids. Our studies have shown that 17 amino acids are suitable for ligation, while Asp, Glu, and Lys are not compatible. Among the working 17 C-terminal amino acids, the retarded reaction resulted from the bulky β-branched amino acid (Thr, Val, and Ile) is not seen under the current ligation condition. We have also investigated the chemoselectivity involving the amino group of the internal lysine which may compete with the N-terminal Ser/Thr for reaction with the C-terminal salicylaldehyde (SAL) ester aldehyde group. The result suggested that the free internal amino group does not adversely slow down the ligation rate.

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Section: Introductionmentioning

confidence: 99%

Realizing serine/threonine ligation: scope and limitations and mechanistic implication thereof

Wong

Lam

et al. 2014

Front. Chem.

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“…We attempted the total chemical synthesis of the regulatory protein HIV‐1 Tat (86 residues) assisted by SCAL16. As shown in Scheme , SCAL was used to link the middle fragment, HIV‐1 Tat(37–60), to the C‐terminal fragment, HIV‐1 Tat(61–86).…”

Section: Limitationsmentioning

confidence: 99%

Scope and limitation of side‐chain assisted ligation

Spasser

Kumar

Brik

2011

Journal of Peptide Science

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“…Thus auxiliary attached to Glu gave the ligation products at a slower rate in comparison to auxiliary attached to Asp. The potential of this ligation method in protein synthesis was verified in the synthesis of HIV‐1 Tat protein27. After successful polypeptide assembly of HIV‐Tat‐1 assisted by SCAL, efforts to remove the auxiliary under different saponification conditions were ineffective.…”

Section: Introductionmentioning

confidence: 99%

Accessing posttranslationally modified proteins through thiol positioning

Kumar

Brik

2010

Journal of Peptide Science

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The field of peptide synthesis achieved considerable advancement in the last decade with the discovery of native chemical ligation (NCL). With the aim of broader application of ligation methods in the synthesis of proteins several strategies have been developed. One of the significant contributions to NCL based strategies is the desulfurization reaction, which removes the thiol handle to generate the unmodified protein. The principle of NCL coupled with desulfurization is effortlessly executed in the synthesis of posttranslationally modified proteins. This short account will cover the recent developments on how new methods of chemical ligation is being evolved and exploited in achieving posttranslationally modified proteins.

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Side-chain assisted ligation in protein synthesis

Cited by 19 publications

References 35 publications

Realizing serine/threonine ligation: scope and limitations and mechanistic implication thereof

Realizing serine/threonine ligation: scope and limitations and mechanistic implication thereof

Scope and limitation of side‐chain assisted ligation

Accessing posttranslationally modified proteins through thiol positioning

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