In Vitro Selection of Functional Lantipeptides | Zendy

Frank T. Hofmann | Zendy; Jack W. Szostak | Zendy; Florian P. Seebeck | Zendy

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In Vitro Selection of Functional Lantipeptides

Author(s) -

Frank T. Hofmann,

Jack W. Szostak,

Florian P. Seebeck

Publication year - 2012

Publication title -

journal of the american chemical society

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 7.115

H-Index - 612

eISSN - 1520-5126

pISSN - 0002-7863

DOI - 10.1021/ja302082d

Subject(s) - chemistry , lanthionine , sortase a , sortase , in vitro , translation (biology) , peptide , staphylococcus aureus , virulence , biochemistry , enzyme , computational biology , combinatorial chemistry , bacterial protein , messenger rna , bacteria , gene , genetics , biology

In this report we present a method to identify functional artificial lantipeptides. In vitro translation coupled with an enzyme-free protocol for posttranslational modification allows preparation of more than 10(11) different lanthionine containing peptides. This diversity can be searched for functional molecules using mRNA-lantipeptide display. We validated this approach by isolating binders toward Sortase A, a transamidase which is required for virulence of Staphylococcus aureus. The interaction of selected lantipeptides with Sortase A is highly dependent on the presence of a (2S,6R)-lanthionine in the peptide and an active conformation of the protein.

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