Application of the OBIMAP (One-Bead Interchain Multipeptide Assembly Platform) to long peptide synthesis: liraglutide as a case study
Author(s)
AlShaer, Danah
Al Musaimi, Othman
Williams, Daryl R
Type
Journal Article
Abstract
This paper reports the application of the recently described OBIMAP (one-bead interchain multipeptide assembly platform) to the synthesis of liraglutide, a representative long peptide (>30 residues), achieving improved yield and purity compared with conventional sequential synthesis. Two synthesis strategies were tested: resin-stapled elongation (RSE) and parallel chain ligation (PCL). RSE, in which two peptide fragments are covalently “stitched” on-resin via orthogonal protection, delivered superior results, up to ∼50% crude purity and 76% recovery versus ∼25% crude purity and 37% recovery for conventional SPPS, while maintained same solvent use as in sequential SPPS. The improved overall purity suggested a reduction in aggregation behavior resulting from the midchain “stitching” step. A current limitation of the process is the extended synthesis time, approximately three times longer than conventional sequential methods, with fragment stitching (linking) representing the most time-consuming step (9–16 h at room temperature). Integration of microwave-assisted fragment linking and automation of three out of nine steps has reduced overall synthesis time to half, while automation of the remaining steps is currently under validation and investigation. The primary challenge for full automation lies in ensuring the compatibility of automated synthesizers with the remaining synthesis steps. Subsequent studies are focused on extending the results obtained at the 0.1 mmol scale to larger production scales (1, 10, and 50 mmol). If successfully implemented at larger scales this strategy, OBIMAP-RSE, could reduce manufacturing costs, enhance accessibility, and accelerate the development of next-generation peptide therapeutics.
Date Issued
2026-04-07
Date Acceptance
2026-03-13
Citation
ACS Omega, 2026, 11 (13), pp.21369-21381
ISSN
2470-1343
Publisher
American Chemical Society
Start Page
21369
End Page
21381
Journal / Book Title
ACS Omega
Volume
11
Issue
13
Copyright Statement
© 2026 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0 .
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41970854
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2026-03-25