scholarly journals Going Round in Circles with N→S Acyl Transfer

Synlett ◽  
2017 ◽  
Vol 28 (13) ◽  
pp. 1517-1529 ◽  
Author(s):  
Derek Macmillan
Keyword(s):  
Transfer Reaction ◽  
Peptide Sequence ◽  
Acyl Transfer ◽  
Native Chemical Ligation ◽  
Full Potential ◽  
Chemical Ligation ◽  
Peptide Engineering ◽  
Naturally Occurring ◽  
Native Peptide ◽  
Peptide Thioesters

It is not highly sophisticated, yet the N→S acyl transfer reaction of a native peptide sequence potentially fills an important technology gap. While several routes to synthetic peptide thioesters exist, only one is routinely applicable for biologically derived samples. Using the naturally occurring amino acid cysteine as the sole activator for N→S acyl transfer we have demonstrated transformation of synthetic and biologically derived precursors into thioesters for use in Native Chemical Ligation, providing a viable alternative for biological samples. Further refinement will be key to realising the full potential of this intriguing process, and increase the number of applications in peptide engineering and therapeutics.1 Introduction2 N→S acyl transfer in ‘normal’ peptide sequences3 Reduced reactivity of internal Xaa-Cys motifs as an advantage in head-to-tail peptide cyclisation4 Reduced reactivity of internal Xaa-Cys motifs as an advantage in modification and cyclisation of biologically produced precursors5 Hydrazinolysis of Xaa-Cys motifs and the acyl hydrazide as a stable thioester equivalent6 Rapid thioester formation via an N→Se acyl shift7 Outlook and conclusions

Acceleration of thiol additive-free native chemical ligation by intramolecular S → S acyl transfer

2015 ◽  
Vol 51 (35) ◽  
pp. 7554-7557 ◽  
Author(s):  
J. Schmalisch ◽  
O. Seitz
Keyword(s):  
Sh3 Domain ◽  
High Reactivity ◽  
Acyl Transfer ◽  
Native Chemical Ligation ◽  
One Pot ◽  
Chemical Ligation ◽  
Synthetic Utility ◽  
Peptide Thioesters

The old dog and a new trick; mercaptopropionylcysteine (MPA–Cys) peptide thioesters show a surprisingly high reactivity in native chemical ligation (NCL) and allow thiol-additive free reactions. This facilitates sequential NCL reactions and ligation–desulfurization reactions in one-pot formats. The synthetic utility is demonstrated by the synthesis of a SH3 domain.

Nucleobase-involved native chemical ligation: a novel reaction between an oxanine nucleobase and N-terminal cysteine for oligonucleotide–peptide conjugation

2020 ◽  
Vol 56 (41) ◽  
pp. 5508-5511
Author(s):  
Eui Kyoung Jang ◽  
Yohei Koike ◽  
Yuko Ide ◽  
Kunihiko Tajima ◽  
Kenji Kanaori ◽  
...  
Keyword(s):  
Transfer Reaction ◽  
Acyl Transfer ◽  
Native Chemical Ligation ◽  
Chemical Ligation ◽  
Site Specific ◽  
Peptide Conjugation ◽  
Acyl Transfer Reaction ◽  
A Site

A novel nucleobase-involved native chemical ligation (NbCL) that allows a site–specific oligonucleotide–peptide conjugation via a new S–N acyl transfer reaction between an oxanine nucleobase and N-terminal cysteine.

scholarly journals Serine promoted synthesis of peptide thioester-precursor on solid support for native chemical ligation

2017 ◽  
Vol 8 (1) ◽  
pp. 117-123 ◽  
Author(s):  
Hader E. Elashal ◽  
Yonnette E. Sim ◽  
Monika Raj
Keyword(s):  
Peptide Synthesis ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Solid Support ◽  
Native Chemical Ligation ◽  
Selective Activation ◽  
Chemical Ligation ◽  
Peptide Thioester ◽  
Peptide Thioesters

Fmoc solid phase peptide synthesis of peptide thioesters by displacement of the cyclic urethane moiety obtained by the selective activation of C-terminal serine.

Derivatized Amino Acids Relevant to Native Peptide Synthesis by Chemical Ligation and Acyl Transfer

2003 ◽  
Vol 68 (24) ◽  
pp. 9247-9254 ◽  
Author(s):  
Derrick L. J. Clive ◽  
Soleiman Hisaindee ◽  
Don M. Coltart
Keyword(s):  
Amino Acids ◽  
Peptide Synthesis ◽  
Acyl Transfer ◽  
Chemical Ligation ◽  
Native Peptide

ChemInform Abstract: Shifting Native Chemical Ligation into Reverse Through N- versus S-Acyl Transfer

ChemInform ◽  
2012 ◽  
Vol 43 (9) ◽  
pp. no-no
Author(s):  
Derek Macmillan ◽  
Anna Adams ◽  
Bhavesh Premdjee
Keyword(s):  
Acyl Transfer ◽  
Native Chemical Ligation ◽  
Chemical Ligation

Access to phosphoproteins and glycoproteins through semi-synthesis, Native Chemical Ligation and N→S acyl transfer

2010 ◽  
Vol 8 (22) ◽  
pp. 5113 ◽  
Author(s):  
Jinit Masania ◽  
Jiejin Li ◽  
Stephen J. Smerdon ◽  
Derek Macmillan
Keyword(s):  
Acyl Transfer ◽  
Native Chemical Ligation ◽  
Chemical Ligation

scholarly journals Amide-forming chemical ligation via O-acyl hydroxamic acids

2018 ◽  
Vol 115 (15) ◽  
pp. 3752-3757 ◽  
Author(s):  
Daniel L. Dunkelmann ◽  
Yuki Hirata ◽  
Kyle A. Totaro ◽  
Daniel T. Cohen ◽  
Chi Zhang ◽  
...  
Keyword(s):  
Peptide Bond ◽  
Amide Bond ◽  
Acyl Transfer ◽  
Medium Size ◽  
Peptide Bonds ◽  
Chemical Ligation ◽  
Native Peptide ◽  
Ligation Product ◽  
Aqueous Conditions ◽  
Acyl Donors

The facile rearrangement of “S-acyl isopeptides” to native peptide bonds via S,N-acyl shift is central to the success of native chemical ligation, the widely used approach for protein total synthesis. Proximity-driven amide bond formation via acyl transfer reactions in other contexts has proven generally less effective. Here, we show that under neutral aqueous conditions, “O-acyl isopeptides” derived from hydroxy-asparagine [aspartic acid-β-hydroxamic acid; Asp(β-HA)] rearrange to form native peptide bonds via an O,N-acyl shift. This process constitutes a rare example of an O,N-acyl shift that proceeds rapidly across a medium-size ring (t1/2 ∼ 15 min), and takes place in water with minimal interference from hydrolysis. In contrast to serine/threonine or tyrosine, which form O-acyl isopeptides only by the use of highly activated acyl donors and appropriate protecting groups in organic solvent, Asp(β-HA) is sufficiently reactive to form O-acyl isopeptides by treatment with an unprotected peptide-αthioester, at low mM concentration, in water. These findings were applied to an acyl transfer-based chemical ligation strategy, in which an unprotected N-terminal Asp(β-HA)-peptide and peptide-αthioester react under aqueous conditions to give a ligation product ultimately linked by a native peptide bond.

scholarly journals Derivatized Amino Acids Relevant to Native Peptide Synthesis by Chemical Ligation and Acyl Transfer.

ChemInform ◽  
2004 ◽  
Vol 35 (13) ◽  
Author(s):  
Derrick L. J. Clive ◽  
Soleiman Hisaindee ◽  
Don M. Coltart
Keyword(s):  
Amino Acids ◽  
Peptide Synthesis ◽  
Acyl Transfer ◽  
Chemical Ligation ◽  
Native Peptide
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