#Biorxiv

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Research May 9, 2026 · View digest

bioRxiv Preprint: AI-Designed Cyclic Peptide CIP-3 Achieves Nanomolar Antagonism of CD28 Immune Checkpoint

A March 2026 bioRxiv preprint reports an AI-guided strategy for the discovery of cyclic peptide antagonists targeting the CD28 immune checkpoint, with the lead candidate CIP-3 binding the CD28 extracellular domain at nanomolar affinity and producing controllable modulation in cellular assays. CD28 is the principal T-cell co-stimulatory receptor and a high-value target for autoimmunity and transplantation, where current biologics (abatacept, belatacept) are large fusion proteins with associated dosing and immunogenicity tradeoffs. CIP-3's small cyclic-peptide format opens the prospect of subcutaneous dosing with a different PK profile. The work illustrates how AI-driven cyclic-peptide design is expanding beyond GLP-1 mimetics into immune-checkpoint pharmacology.

Research May 3, 2026 · View digest

bioRxiv (May 1): Generative AI Designs Peptides with Custom Secondary Structure Motifs Using Reduced Amino-Acid Alphabets

A May 1 bioRxiv preprint introduces a generative AI protein-design model trained on hundreds of thousands of structures from the RCSB PDB to produce peptides with custom secondary structure motifs while operating on reduced amino-acid alphabets. The work targets a real bottleneck in cyclic peptide drug development — generating sequences that fold into specified secondary-structure scaffolds without exhausting the full 20-letter design space, which lowers the barrier for synthesis and downstream maturation. It joins the recent University of Utah PapB enzymatic cyclization paper, the Nature Communications few-shot AI Acinetobacter pipeline, and Profluent's recombinase work as part of the broader AI-peptide-design wave through April–May 2026.