10sg
The CryoEM structure of T12 type1 nanofiber
Structural highlights
Publication Abstract from PubMedThe 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 (64)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. Tailoring Avidity through Morphology: Structure-Avidity Relationship in CD38-Binding Nanofiber Radiotracers.,Godbe JM, Zhang H, Sharma AK, Ernst KN, Jing Z, Dyer MR, Prior JL, Teubner E, Manion B, Tang R, Yang Y, Shokeen M ACS Appl Bio Mater. 2026 May 4;9(9):4242-4257. doi: 10.1021/acsabm.6c00348. Epub , 2026 Apr 21. PMID:42011845[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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