Butelase 1: A Versatile Ligase for Peptide and Protein Macrocyclization

• Published in: Journal of the American Chemical Society Vol. 137; no. 49; pp. 15398 - 15401
• Main Authors: Nguyen, Giang K. T, Kam, Antony, Loo, Shining, Jansson, Anna E, Pan, Lucy X, Tam, James P
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 16.12.2015; Amer Chemical Soc
• Subjects: Amino Acid Sequence; Animals; Chemistry; Chemistry, Multidisciplinary; Cyclization; drugs; Humans; Ligases - chemistry; Ligases - metabolism; Models, Molecular; Molecular Sequence Data; Peptide Synthases - chemistry; Peptide Synthases - genetics; Peptide Synthases - metabolism; peptides; Peptides - chemistry; Peptides - metabolism; Physical Sciences; Plant Proteins - chemistry; Plant Proteins - genetics; Plant Proteins - metabolism; protein engineering; proteins; Proteins - chemistry; Proteins - metabolism; Rats; Science & Technology; sortase A; CYCLOTIDES; IMPROVE; BIOSYNTHESIS; LIGATION; SORTASE; BACKBONE; PRECURSORS; CYCLIC-PEPTIDES; CYCLIZATION; FAMILY
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/jacs.5b11014

Macrocyclization is a valuable tool for drug design and protein engineering. Although various methods have been developed to prepare macrocycles, a general and efficient strategy is needed. Here we report a highly efficient method using butelase 1 to macrocyclize peptides and proteins ranging in sizes from 26 to >200 residues. We achieved cyclizations that are 20,000 times faster than sortase A, the most widely used ligase for protein cyclization. The reactions completed within minutes with up to 95% yields.