Biomaterial Database

Irreversible sortase A-mediated ligation driven by diketopiperazine formation. 2014

Fa Liu, and Ethan Y Luo, and David B Flora, and Adam R Mezo

Lilly Research Laboratories , Indianapolis, Indiana 46285, United States.

Sortase A (SrtA)-mediated ligation has emerged as an attractive tool in bioorganic chemistry attributing to the remarkable specificity of the ligation reaction and the physiological reaction conditions. However, the reversible nature of this reaction limits the efficiency of the ligation reaction and has become a significant constraint to its more widespread use. We report herein a novel set of SrtA substrates (LPETGG-isoacyl-Ser and LPETGG-isoacyl-Hse) that can be irreversibly ligated to N-terminal Gly-containing moieties via the deactivation of the SrtA-excised peptide fragment through diketopiperazine (DKP) formation. The convenience of the synthetic procedure and the stability of the substrates in the ligation buffer suggest that both LPETGG-isoacyl-Ser and LPETGG-isoacyl-Hse are valuable alternatives to existing irreversible SrtA substrate sequences.

UI	MeSH Term	Description	Entries
D003546	Cysteine Endopeptidases	ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
D001426	Bacterial Proteins	Proteins found in any species of bacterium.	Bacterial Gene Products,Bacterial Gene Proteins,Gene Products, Bacterial,Bacterial Gene Product,Bacterial Gene Protein,Bacterial Protein,Gene Product, Bacterial,Gene Protein, Bacterial,Gene Proteins, Bacterial,Protein, Bacterial,Proteins, Bacterial
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor
D015394	Molecular Structure	The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.	Structure, Molecular,Molecular Structures,Structures, Molecular
D054659	Diketopiperazines	Piperazines with two keto oxygens.	Diketopiperazine Compounds,Diketopiperazine,Diketopiperazine Ion (1-),Piperazinediones,Pyrrolodiketopiperazines,Pyrrolopiperazinediones
D019881	Aminoacyltransferases	Enzymes that catalyze the transfer of an aminoacyl group from donor to acceptor resulting in the formation of an ester or amide linkage. EC 2.3.2.