Chemical Synthesis and Analysis

Automated DNA-Encoded Library Synthesis on Magnetic Anion Exchange Resin

This paper automates DNA-encoded library synthesis using magnetic anion exchange resin and a particle-handling instrument, enabling efficient and scalable DEL production.

De novo macrocyclic peptide discovery produces potent class A GPCR ligands with diverse pharmacology

This study discovers potent, selective macrocyclic peptide ligands for CXCR4, a class A GPCR, demonstrating the feasibility of de novo peptide design for this receptor family.

β-Hairpin Fold Peptide Brush Polymers

This study examines peptide-brush polymers mimicking protein structure, finding that polymer backbones disrupt secondary structures and alter free-energy landscapes.

A scalable recombinant pipeline for disulphide-stapled peptides

This paper describes a scalable recombinant pipeline for producing disulphide-stapled cyclic peptides, achieving high yields and enabling high-throughput screening.

Pair-complete structural gating enables Pareto optimization of de novo cyclic peptides with preserved binding geometry and improved developability

This paper introduces RF-PepTune, a method that improves cyclic peptide design by preserving binding geometry while optimizing multiple properties, achieving higher success rates in structural and functional criteria.

A Two-Step Synthesis of Covalent Genetically-Encoded Libraries of Peptide-Derived Macrocycles (cGELs) enables use of electrophiles with diverse reactivity

This paper develops a two-step synthesis method for covalent genetically-encoded libraries of peptide-derived macrocycles (cGELs) that enables the use of electrophiles with diverse reactivity by controlling reaction conditions.

De novo design of small cyclic peptide inhibitors from non-canonical amino acids by cofolding-guided search

This paper introduces nCycle-Forge, a computational method for designing cyclic peptides that outperforms existing approaches in hit rate and potency against two targets.

The hydrophobicity of peptides limits their availability to bind to interacting domains

The paper identifies that peptide hydrophobicity affects their availability in yeast cells, impacting synthetic interaction strength beyond in vitro measurements.

Random in vitro Protein single-Loop Engineering (RiPLE) by mRNA display

This paper introduces RiPLE, a method for discovering engineered protein binders, and shows it produces high-affinity, selective binders for ROR1 and GS.

Genetically-encoded discovery and development of peptide-macrocycle imaging agents for PD-L1

This paper develops PD-L1-targeting macrocycle imaging agents using phage-display technology without non-canonical amino acids, achieving single-digit-nanomolar potency and structural characterization.

Expanding Macrocyclic Topology through Cysteine-to-N-Terminal Cyclisation Enables Covalent Peptide Inhibitor Discovery

This paper introduces a new cyclisation strategy using a bromomethyl picolinaldehyde linker to expand macrocyclic peptide topologies, leading to more potent and diverse inhibitors.

Improved Protein Semi-Synthesis Enables Biophysical Studies of Thioamide Destabilization of β-Sheet Interactions

This paper develops a method to synthesize thioamide-containing proteins and shows they destabilize β-sheet structures in GB1 and α-synuclein fibrils.

PANCS-Inhibitors: A rapid method to directly select for protein-protein interaction inhibitors

PANCS-Inhibitors rapidly selects molecules that directly disrupt pre-formed protein-protein interactions, demonstrating effectiveness against three oncogenic PPIs.

Total synthesis and structural characterization of a novel protein scaffold from the snail Biomphalaria glabrata.

This study synthesizes and characterizes a novel disulfide-rich miniprotein scaffold from Biomphalaria glabrata, revealing its structure, stability, and spatial expression.

Discovery of an NRAS isoform and activation-state selective macrocyclic peptide

The paper identifies a macrocyclic peptide that selectively binds NRAS with isoform and activation-state specificity, but lacks membrane permeability and functional inhibition.

Total Synthesis of Self-Assembling Semi-Synthetic Proteins Utilizing a Dendritic Solubility Tag

This paper introduces a covalent tagging strategy to solubilize hydrophobic probes for bioconjugation, enabling the synthesis of self-assembling semi-synthetic proteins.

GALILEO: Embodied AI scientist for autonomous therapeutic discovery in dynamic membrane systems

GALILEO autonomously discovers therapeutic peptides by combining AI reasoning with lab experiments, identifying peptides that block membrane currents and modulate immune responses.

Accurate de novo design of peptides from programming biophysical landscape

NeoPep designs functional peptides de novo using a deep-learning framework that models biophysical principles, achieving high hit rates and structural accuracy across diverse targets.

PepForge: Hierarchical HELM-Based Peptide Generation

PepForge generates modified peptides using HELM notation and a deep learning model, producing novel antimicrobial peptides.

AI-designed cyclic peptides enable controllable modulation of the CD28 immune checkpoint

This paper designs AI-generated cyclic peptides that modulate the CD28 immune checkpoint with controllable pharmacology and therapeutic efficacy in preclinical models.

De novo designed cyclic MC4R peptide agonist reduces food intake in mice

The paper designs a cyclic MC4R peptide agonist using deep learning and validates its efficacy in reducing food intake in mice.

Mirror-image mRNA display uncovers isoform-selective D-peptide macrocycles targeting a cryptic KRAS pocket

This paper uses mirror-image mRNA display to discover D-peptide macrocycles targeting a new KRAS binding site, showing selectivity and efficacy in inhibiting KRAS-mutant cells.

De novo design of a macrocycle induced dimerization system for cellular control

This paper designs a chemically induced dimerization system using a de novo macrocycle and protein homodimer to control cellular processes.

Thermal-Acoustic Activation of Hydrophobic Polystyrene Supports for High-Efficiency Aqueous Solid-Phase Peptide Synthesis

This paper demonstrates a thermal-acoustic method for aqueous solid-phase peptide synthesis on hydrophobic polystyrene resins, achieving high efficiency and purity.

Reversible CD28 checkpoint modulation by cyclic peptides outperforms biologic blockade under exposure-limited conditions

This study introduces CP8, a cyclic peptide that effectively blocks CD28 co-stimulation and allows rapid restoration of T-cell function, outperforming existing biologics under exposure-limited conditions.

Computational Design and Biophysical Validation of Macrocyclic Peptides as Inhibitors of SLIT2/ROBO1 interaction

This paper computationally designs and experimentally validates macrocyclic peptides that inhibit SLIT2/ROBO1 interaction, showing promising in vitro properties.

Mapping the Modification Landscape of MHC-I Epitopes: A Framework for Immunogenic Peptidomimetic Antigen Design

This paper evaluates peptidomimetic modifications of MHC-I epitopes to improve antigen design, finding position-dependent tolerance and non-additive effects on immunogenicity and pharmacokinetics.

Uncovering cancer dependencies in peptide-interacting protein pockets

The paper screens peptide-binding pockets across cancer cell lines to identify therapeutic vulnerabilities and dependencies, finding that peptide inhibition can reveal hidden dependencies and enhance drug efficacy.

Cyclic peptides space: The methodology of sequence selection to cover the comprehensive physical properties

The paper introduces a methodology to generate cyclic peptide libraries with uniform coverage of physicochemical properties using a protein language model and cyclic permutation averaging.

An Integrated Biophysical Fragment Screening Approach Identifies Novel Binders of the CD28 Immune Receptor

This paper uses fragment-based screening to identify small molecules that bind to the CD28 receptor, demonstrating a successful approach for targeting its PPI interface.