Synthesis and use of a pseudo-cysteine for native chemical ligation.
The process of native chemical ligation (NCL) is well described in the literature. An N-terminal cysteine-containing peptide reacts with a C-terminal thioester-containing peptide to yield a native amide bond after transesterification and acyl transfer. An N-terminal cysteine is required as both the N-terminal amino function and the sidechain thiol participate in the ligation reaction. In certain circumstances it is desirable, or even imperative, that the N-terminal region of a peptidic reaction partner remain unmodified, for Instance for the retention of biological activity after ligation. This work discusses the synthesis of a pseudo-N-terminal cysteine building block for incorporation into peptides using standard methods of solid phase synthesis. Upon deprotection, this building block affords a de facto N-terminal cysteine positioned on an amino acid sidechain. which is capable of undergoing native chemical ligation with a thioester. The syntheses of several peptides and structures containing this motif are detailed, their reactions discussed. and further applications of this technology proposed.
Alves
David A
DA
Adprotech Ltd. Chesterford Research Park, Little Chesterford, Saffron Walden, Essex CB10 1XL UK.
Esser
Dirk
D
Broadbridge
Robert J
RJ
Beevers
Andrew P G
AP
Chapman
Christopher P
CP
Winsor
Clare E
CE
Betley
Jason R
JR
D000595:Amino Acid Sequence; D003545:Cysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis*
D008164:Luminescent Proteins; D010455:Peptides; D049452:Green Fluorescent Proteins; D003545:Cysteine