Journal Article

DKFZ-2026-00236

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png High Yield Branched Puromycin Linker Design Enables Efficient cDNA Display and Chemical Modification of Peptides.

Schneider, S.DKFZ* ; Boll, M.DKFZ* ; Eder, M.DKFZ* ; Eder, A.-C.DKFZ*

2026
Wiley New York, NY [u.a.]

Abstract: Peptide chemical modification is a valuable technique for improving peptide stability and bioactivity, particularly in drug discovery applications. Here, we report the development of a novel linker junction strategy using strain-promoted azide-alkyne cycloaddition (SPAAC) that enables the efficient formation of branched puromycin linkers with an average yield of 97%. This approach represents an improvement over traditional Michael-Addition methods, which typically yield ~15%-20%. The high yield of the SPAAC reaction and the near absence of by-products make the linkage by click reaction easy to purify. We demonstrate the utility of our linker design by successfully performing cDNA display and chemical modification strategies such as bicyclization of peptides. Our study demonstrates the functionality of the cDNA display system with the newly incorporated junction. In addition, the successful introduction of peptide bicyclization via tris-bromomethyl-benzene (TBMB) in cDNA display serves as a proof-of-concept for complex chemical modifications. Furthermore, the position of puromycin, which disrupts protein biosynthesis, has been determined. This approach offers novel insights into the discovery of chemically modified peptides and has the potential to accelerate the development of peptide-based therapeutics and diagnostics.

Keyword(s): EpCAM ; SPAAC ; bicyclic peptides ; cDNA‐display ; puromycin linker ; therapeutic peptides

Note: #DKTKZFB26# / 2026 May;123(5):1399-1404

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Freiburg (FR01)
2. DKTK FR Radiopharmazeutische Entwicklung (FR03)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

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Database coverage:
; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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