Semisynthesis of Human Ribonuclease-S.


Journal

Bioconjugate chemistry
ISSN: 1520-4812
Titre abrégé: Bioconjug Chem
Pays: United States
ID NLM: 9010319

Informations de publication

Date de publication:
20 01 2021
Historique:
pubmed: 10 12 2020
medline: 15 9 2021
entrez: 9 12 2020
Statut: ppublish

Résumé

Since its conception, the ribonuclease S complex (RNase S) has led to historic discoveries in protein chemistry, enzymology, and related fields. Derived by the proteolytic cleavage of a single peptide bond in bovine pancreatic ribonuclease (RNase A), RNase S serves as a convenient and reliable model system for incorporating unlimited functionality into an enzyme. Applications of the RNase S system in biomedicine and biotechnology have, however, been hindered by two shortcomings: (1) the bovine-derived enzyme could elicit an immune response in humans, and (2) the complex is susceptible to dissociation. Here, we have addressed both limitations in the first semisynthesis of an RNase S conjugate derived from human pancreatic ribonuclease and stabilized by a covalent interfragment cross-link. We anticipate that this strategy will enable unprecedented applications of the "RNase-S" system.

Identifiants

pubmed: 33296182
doi: 10.1021/acs.bioconjchem.0c00557
pmc: PMC7856262
mid: NIHMS1654238
doi:

Substances chimiques

Ribonucleases EC 3.1.-
Ribonuclease, Pancreatic EC 3.1.27.5
ribonuclease S EC 3.1.4.-

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

82-87

Subventions

Organisme : NCI NIH HHS
ID : R01 CA073808
Pays : United States

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Auteurs

Jessica Sayers (J)

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

Evans C Wralstad (EC)

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

Ronald T Raines (RT)

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

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Classifications MeSH