ArticleProceedings of the National Academy of Sciences of the United States of America2016
Programmable polyproteams built using twin peptide superglues.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers.
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Who cites it
145 citing papers in PubMed, 352 citations in OpenAlex.
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- Rational Design and One-Step Immobilization of Chitosanase for Specific and Recyclable Chitobiose Production.Foods (Basel, Switzerland) · 2025Article
- Boolean logic-gated protein presentation through autonomously compiled molecular topology.Nature chemical biology · 2025Article
- Protein nanocages: A new frontier in mucosal vaccine delivery and immune activation.Human vaccines & immunotherapeutics · 2025Review
- Advances in Nanobody-Based Platforms for Precision Cancer Diagnosis and Therapy.Polymer science & technology (Washington, D.C.) · 2025Review
85 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Programmed connection of amino acids or nucleotides into chains introduced a revolution in control of biological function. Reacting proteins together is more complex because of the number of reactive groups and delicate stability. Here we achieved sequence-programmed irreversible connection of protein units, forming polyprotein teams by sequential amidation and transamidation. SpyTag peptide is engineered to spontaneously form an isopeptide bond with SpyCatcher protein. By engineering the adhesin RrgA from Streptococcus pneumoniae, we developed the peptide SnoopTag, which formed a spontaneous isopeptide bond to its protein partner SnoopCatcher with >99% yield and no cross-reaction to SpyTag/SpyCatcher. Solid-phase attachment followed by sequential SpyTag or SnoopTag reaction between building-blocks enabled iterative extension. Linear, branched, and combinatorial polyproteins were synthesized, identifying optimal combinations of ligands against death receptors and growth factor receptors for cancer cell death signal activation. This simple and modular route to programmable "polyproteams" should enable exploration of a new area of biological space.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.