A general route for post-translational cyclization of mRNA display libraries.
Cyclic peptides are attractive scaffolds for the design of conformationally constrained molecular therapeutics. Previously, biological display libraries could only be cyclized via disulfide bonds, which are labile and can be reduced in an intracellular environment. In this paper, we construct high diversity, covalently cyclized mRNA display libraries (>1013 sequences) and analyze the cyclization reaction using MALDI-TOF MS and unnatural amino acid incorporation. Our route allows the extent of cyclization to be evaluated quantitatively and is broadly applicable to a variety of cyclization chemistries.
Millward
Steven W
SW
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Takahashi
Terry T
TT
Roberts
Richard W
RW
D003500:Cyclization; D015394:Molecular Structure; D020411:Oligonucleotide Array Sequence Analysis; D019151:Peptide Library; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000737:chemistry*; D012260:Ribonucleases / Q000737:chemistry
D019151:Peptide Library; D012333:RNA, Messenger; D012260:Ribonucleases