Rapid additive-free selenocystine-selenoester peptide ligation.
We describe an unprecedented reaction between peptide selenoesters and peptide dimers bearing N-terminal selenocystine that proceeds in aqueous buffer to afford native amide bonds without the use of additives. The selenocystine-selenoester ligations are complete in minutes, even at sterically hindered junctions, and can be used in concert with one-pot deselenization chemistry. Various pathways for the transformation are proposed and probed through a combination of experimental and computational studies. Our new reaction manifold is also showcased in the total synthesis of two proteins.
School of Chemistry, The University of Sydney , Sydney, NSW 2006, Australia.
Nicholas J
NJ
Mitchell
School of Chemistry, The University of Sydney , Sydney, NSW 2006, Australia.
Lara R
LR
Malins
School of Chemistry, The University of Sydney , Sydney, NSW 2006, Australia.
Xuyu
X
Liu
School of Chemistry, The University of Sydney , Sydney, NSW 2006, Australia.
Robert E
RE
Thompson
School of Chemistry, The University of Sydney , Sydney, NSW 2006, Australia.
Bun
B
Chan
School of Chemistry, The University of Sydney , Sydney, NSW 2006, Australia.
Leo
L
Radom
School of Chemistry, The University of Sydney , Sydney, NSW 2006, Australia.
Richard J
RJ
Payne
D000942:Antigens, Bacterial / Q000737:chemistry; D001426:Bacterial Proteins / Q000138:chemical synthesis* / Q000737:chemistry; D002826:Chorismate Mutase / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D003553:Cystine / Q000031:analogs & derivatives* / Q000737:chemistry; D004952:Esters / Q000737:chemistry; D008968:Molecular Conformation; D009169:Mycobacterium tuberculosis / Q000201:enzymology; D016566:Organoselenium Compounds / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D018036:Selenium Compounds / Q000737:chemistry
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D004952:Esters; D016566:Organoselenium Compounds; D010455:Peptides; D018036:Selenium Compounds; C009226:selenocystine; D003553:Cystine; D002826:Chorismate Mutase