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 d...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Journal of the American Chemical Society 2005-10, Vol.127 (41), p.14142-14143
Hauptverfasser:	Millward, Steven W, Takahashi, Terry T, Roberts, Richard W
Format:	Artikel
Sprache:	eng
Schlagworte:	Biological and medical sciences Cyclization Fundamental and applied biological sciences. Psychology Miscellaneous Molecular biophysics Molecular Structure Oligonucleotide Array Sequence Analysis Peptide Library Physical chemistry in biology Protein Processing, Post-Translational Ribonucleases - chemistry RNA, Messenger - chemistry
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	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.
ISSN:	0002-7863 1520-5126
DOI:	10.1021/ja054373h