Orthogonal ligation: a three piece assembly of a PNA–peptide–PNA conjugate

Burlina, Fabienne; Dixson, David D.; Doyle, Robert P.; Chassaing, Gérard; Boddy, Christopher N.; Dawson, Philip E.; Offer, John

doi:10.1039/b801242c

Cited by 8 publications

(10 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The observation that strongly nucleophilic thiol additives can suppress the ligation of the 2‐mercaptobenzyl class of auxiliaries was used to regiospecifically ligate a PNA thioester onto cysteine attached to a lysine side‐chain in the presence of unprotected auxiliary 10 (Figure 7), its nucleophilicity masked by the benzylmercaptan 64. This was followed by an orthogonal trimethoxybenzyl 10 ‐mediated ligation to sequentially synthesize a PNA‐peptide‐PNA conjugate with an isopeptide bond (Figure 7).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Native chemical ligation with N^α acyl transfer auxiliaries

Offer

2010

Biopolymers

Self Cite

View full text Add to dashboard Cite

Native chemical ligation (NCL) is a simple procedure that enables synthetic access to many proteins and is increasingly harnessed to study protein structure and function. However, the generality of this method is limited by the requirement for cysteine residues suitably positioned throughout the target protein. Auxiliary approaches have been developed to overcome this limitation, wherein a removable group is introduced at the amino terminus of a peptide conveying ligation properties comparable to cysteine. Present auxiliary approaches combine the thioester exchange concept applied first in NCL with a number of acyl transfer reactions first systematically explored by Kemp and coworkers. The current methods for auxiliary mediated ligation appear promising for the synthesis of proteins and in particular post-translational modified proteins.

show abstract

Section: Introductionmentioning

confidence: 99%

“… The use of the trimethoxybenzyl auxiliary 10 for an orthogonal amide ligation strategy, regio‐specific amide bond ligation with three components and no protecting groups 64. The addition of benzylmercaptan in the first ligation prevents ligation at the auxiliary, masking its nucleophilicity.…”

Section: Introductionmentioning

confidence: 99%

Native chemical ligation with N^α acyl transfer auxiliaries

Offer

2010

Biopolymers

Self Cite

View full text Add to dashboard Cite

show abstract

“…Firstly, PNA synthesis is mostly like peptide synthesis using commercial available PNA monomers by the widely used Boc or Fmoc SPPS. Secondly, with its peptide-like features, PNA can be ligated to another peptide by chemical ligation methods 13,14 in place of the complicated biotin-streptavidin coupling system for conjugation between the DNA and protein. Thirdly, the complementary PNA/PNA can be bound by parallel mode, which can simplify the procedures to prepare PNA-peptide conjugates.…”

Section: Specific Disulfide Bond Formation Directed By Peptide Nucleimentioning

confidence: 99%

Specific Disulfide Bond Formation Directed by Peptide Nucleic Acids

Cai

Hou

2020

J. Braz. Chem. Soc.

View full text Add to dashboard Cite

In this study, we successfully demonstrated a strategy for specific disulfide bond formation by hybridization of two complementary peptide nucleic acid strands. Peptides were linked to the pair of complementary peptide nucleic acids by native chemical ligation, respectively, and base pairing drove the two peptides into close proximity for interchain disulfide bond formation. Since peptide nucleic acids directed system is easier to manipulate than deoxyribonucleic acid system, this system will be more useful and have a broader application scope in the construction of complex biomolecular structures.

show abstract

“…Such an orthogonal ligation was first realized by Offer and coworkers in the context of a peptide‐PNA ligation 31. The thioesters for that study had been prepared using Boc chemistry and we additionally aimed to explore compatibility between EL, thioester production via an N → S acyl shift, and using Fmoc/ t Bu chemistry throughout 32, 33.…”

Section: Introductionmentioning

confidence: 99%

Towards biomolecular assembly employing extended native chemical ligation in combination with thioester synthesis using an N→S acyl shift

2010

View full text Add to dashboard Cite

The advent of kinetically controlled Native Chemical Ligation has permitted more efficient sequential Native Chemical Ligation reactions to take place in one pot where one or more of the peptide fragments contains an N-terminal cysteine residue and a C-terminal thioester. The reactivity of the thioester component can dictate how fragments behave through careful choice of leaving group (alkyl or aryl thiol) and the C-terminal amino acid residue. Although thioester reactivity is exquisitely controlled, reactivity of the N-terminal cysteine residue has been curbed using protecting groups, usually the thiazolidine-4-carboxo (Thz) group as it can be removed in the presence of the thioester at acidic pH. Only recently has the concept of orthogonal ligation been extended to thiol auxiliary mediated Native Chemical Ligation (a.k.a. Extended Ligation) which, owing to their inherent difference in reactivity, have allowed peptides to be selectively extended at the C-terminus without recourse to protecting groups on the N-terminus. Herein we explored the compatibility of acyl transfer auxiliaries with peptide thioester production via an N-->S acyl shift for this purpose.

show abstract

Orthogonal ligation: a three piece assembly of a PNA–peptide–PNA conjugate

Abstract: A PNA-peptide-PNA conjugate was assembled from three fragments using a combination of native chemical ligation and an orthogonal, auxiliary-mediated ligation.

Cited by 8 publications

References 28 publications

Native chemical ligation with N^α acyl transfer auxiliaries

Native chemical ligation with N^α acyl transfer auxiliaries

Specific Disulfide Bond Formation Directed by Peptide Nucleic Acids

Towards biomolecular assembly employing extended native chemical ligation in combination with thioester synthesis using an N→S acyl shift

Contact Info

Product

Resources

About

Orthogonal ligation: a three piece assembly of a PNA–peptide–PNA conjugate

Abstract: A PNA-peptide-PNA conjugate was assembled from three fragments using a combination of native chemical ligation and an orthogonal, auxiliary-mediated ligation.

Cited by 8 publications

References 28 publications

Native chemical ligation with Nα acyl transfer auxiliaries

Native chemical ligation with Nα acyl transfer auxiliaries

Specific Disulfide Bond Formation Directed by Peptide Nucleic Acids

Towards biomolecular assembly employing extended native chemical ligation in combination with thioester synthesis using an N→S acyl shift

Contact Info

Product

Resources

About

Native chemical ligation with N^α acyl transfer auxiliaries

Native chemical ligation with N^α acyl transfer auxiliaries