Solid-Phase Synthesis of Megamolecules

Blaise R. Kimmel, Justin A. Modica, Kelly Parker, Vinayak Dravid, Milan Mrksich*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


This paper presents a solid-phase strategy to efficiently assemble multiprotein scaffolds - known as megamolecules - without the need for protecting groups and with precisely defined nanoscale architectures. The megamolecules are assembled through sequential reactions of linkers that present irreversible inhibitors for enzymes and fusion proteins containing the enzyme domains. Here, a fusion protein containing an N-terminal cutinase and a C-terminal SnapTag domain react with an ethyl p-nitrophenyl phosphonate (pNPP) or a chloro-pyrimidine (CP) group, respectively, to give covalent products. By starting with resin beads that are functionalized with benzylguanine, a series of reactions lead to linear, branched, and dendritic structures that are released from the solid support by addition of TEV protease and that have sizes up to approximately 25 nm.

Original languageEnglish (US)
Pages (from-to)4534-4538
Number of pages5
JournalJournal of the American Chemical Society
Issue number10
StatePublished - Mar 11 2020

ASJC Scopus subject areas

  • General Chemistry
  • Biochemistry
  • Catalysis
  • Colloid and Surface Chemistry


Dive into the research topics of 'Solid-Phase Synthesis of Megamolecules'. Together they form a unique fingerprint.

Cite this