Rapid Chemical Synthesis of Neuroprotective Hi1a
The Pentelute Lab aims to invent new chemistry for the efficient and selective modification of proteins, to ‘hijack’ these biological machines for efficient drug delivery into cells and to create new machines to rapidly and efficiently manufacture peptides and proteins.
Pentelute Lab, Chemistry, MIT, Chemistry Department, Boston, Cambridge, Biology, Peptides, Peptide, Proteins, Science, Rapid, Brad Pentelute, Brad,
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Rapid Chemical Synthesis of Neuroprotective Hi1a

Rapid Chemical Synthesis of Neuroprotective Hi1aClick to copy article link

Stephen A. Byrne, Giulio Fittolani, Elee Shimshoni, Charlotte E. Farquhar, Julien Couture-Senécal, Andrei Loas, Daniel G. Anderson, Bradley L. Pentelute

Abstract

Hi1a is a venom peptide isolated from the Australian funnel-web spider Hadronyche infensa, containing an intricate “double knot” tertiary structure, and is currently under investigation for the treatment of ischemic stroke. The recombinant expression and chemical synthesis of Hi1a remain a significant challenge due to laborious protocols, delaying progress in translation to the clinic. We describe the first single-shot chemical synthesis of Hi1a (76 amino acids, AA) using automated fast-flow peptide synthesis (AFPS), enabling rapid access (10 mg). This work highlights the utility of AFPS as a technology that enables chemical production of biomolecules challenging to obtain by recombinant methods.

Category
2025, Publications