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TitleTailoring Avidity through Morphology: Structure-Avidity Relationship in CD38-Binding Nanofiber Radiotracers.
Journal, issue, pagesACS Appl Bio Mater, Vol. 9, Issue 9, Page 4242-4257, Year 2026
Publish dateMay 4, 2026
AuthorsJacqueline M Godbe / Hongwei Zhang / Amit K Sharma / Katelyn N Ernst / Zhenghan Jing / Michael R Dyer / Julie L Prior / Erin Teubner / Brad Manion / Rui Tang / Yang Yang / Monica Shokeen /
PubMed AbstractThe lack of targeted molecular imaging agents for multiple myeloma (MM) hinders precise disease characterization and theranostic development. We address this by engineering a tunable platform of self- ...The lack of targeted molecular imaging agents for multiple myeloma (MM) hinders precise disease characterization and theranostic development. We address this by engineering a tunable platform of self-assembled peptide nanofibers that target CD38, a key antigen in MM. Simple variation of a conjugated lipid tail length (C4-C12) dictates the supramolecular architecture, as revealed by high-resolution cryo-EM. This structural control directly modulates biological function: avidity for CD38 increases monotonically with tail length, culminating in T12 nanofibers with sub-nanomolar affinity. This optimized morphology also enables unique pH-responsive di-tyrosine cross-linking and, critically, facilitates polyvalent cell-surface engagement that outcompetes high-affinity monomers in vitro. The nanofibers are efficiently radiolabeled with Cu, exhibit exceptional serum stability, and show no toxicity at doses 20-fold above projected imaging use. By establishing lipid tail length as a simple, powerful handle for controlling nanofiber structure, avidity, and function, we present a robust, translatable platform for advancing targeted imaging and therapy in CD38-positive malignancies.
External linksACS Appl Bio Mater / PubMed:42011845
MethodsEM (helical sym.)
Resolution2.84 - 3.11 Å
Structure data

75431

10sd

EMDB-75431, PDB-10sd:
The cryoEM structure of T10 type2 nanofiber
Method: EM (helical sym.) / Resolution: 3.11 Å

75434

10sg

EMDB-75434, PDB-10sg:
The CryoEM structure of T12 type1 nanofiber
Method: EM (helical sym.) / Resolution: 2.84 Å

75435

10sh

EMDB-75435, PDB-10sh:
The CryoEM structure of T12 type2 nanofiber
Method: EM (helical sym.) / Resolution: 2.97 Å

Chemicals

ChemComp-DKA:
DECANOIC ACID

ChemComp-DAO:
LAURIC ACID

Source
  • synthetic construct (others)
KeywordsPROTEIN FIBRIL / nanofiber

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