Chemical Synthesis and Analysis

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.

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.

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.

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 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.

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.

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.

Macrocyclic Peptides Containing an Imidazopyridinium (IP+) Unit Display Enhanced Passive Cell Permeability

This study shows that adding an imidazopyridinium (IP+) unit to macrocyclic peptides enhances their passive membrane permeability, enabling them to enter cells and inhibit intracellular targets like p53-MDM2.

Systematic profiling of peptide substrate specificity in N-terminal processing by methionine aminopeptidase using mRNA display and an unnatural methionine analogue

The paper systematically profiles MAP substrate specificity using mRNA display and N-terminal Met analogues, revealing residue impacts on cleavage efficiency.

Examining Selection Dynamics and Limitations in Multi-round Protein Selection of High Diversity Libraries

The paper presents analyses to assess selection dynamics in multi-round protein selection experiments, offering insights into diversity, coverage, and reproducibility.

Simple synthesis and functionalisation of α-hydroxyglycine-containing peptide fragments

The paper describes a simple chemical synthesis method for Fmoc-protected α-hydroxyglycine dipeptides and demonstrates their functionalization with non-natural amino acids.

Minimal N-methylated and stapled peptide ligands for the autophagy protein GABARAP

This paper develops N-methylated and stapled peptide ligands for GABARAP with low nanomolar affinity and subfamily selectivity.

AI-Guided Design of Cyclic Peptide Binders Targeting TREM2 Using CycleRFdiffusion and Experimental Validation

The paper designs cyclic peptides targeting TREM2 using AI tools and validates their binding and stability.

Sequence engineering at non-motif modulator residues yields a peptide that effectively targets a single PDZ protein in a disease-relevant cellular context

The paper engineers a peptide that selectively targets a single PDZ domain in a cystic fibrosis model, enhancing chloride efflux.

Enhancing the efficacy, utility and throughput of the Transcription Block Survival peptide library screening platform

The paper enhances the Transcription Block Survival (TBS) platform to improve throughput, simplify target switching, and increase selection stringency for discovering peptide inhibitors of protein-DNA interactions.

Chemokine-binding all-D-CLIPS™ peptides identified using mirror-image phage display

This study identifies chemokine-binding all-D-CLIPS™ peptides using mirror-image phage display, showing sub-micromolar affinity and structural diversity.

Peptide Design through Binding Interface Mimicry

PepMimic, an all-atom latent diffusion model guided by a contrastive interface encoder, designs peptides mimicking known binders; 8% of tested peptides across five targets reached 10^-8M KD.

A Functional Assay For Mining Non-Inhibitory Enzyme Ligands From One Bead One Compound Libraries: Application to E3 Ubiquitin Ligases

The paper introduces a functional assay to identify non-inhibitory enzyme ligands from bead-displayed compound libraries, applied to E3 ubiquitin ligases, and discovers a novel ligand for VHL.

Decoding protein-peptide interactions using a large, target-agnostic yeast surface display library

The paper develops a large yeast surface display library to identify high-affinity peptide ligands for various protein targets, revealing binding motifs and novel clones.

De novo design and structure of a peptide-centric TCR mimic binding module

A de novo four-helix bundle designed with RFdiffusion and ProteinMPNN binds NY-ESO-1/HLA-A*02 at Kd 9.5 nM, with a 2.05 Å crystal structure and peptide-focused docking.

Engineered reactivity of a bacterial E1-like enzyme enables ATP-driven modification of protein C termini

The paper develops an ATP-driven platform for C-terminal protein modification using a bacterial E1-like enzyme, enabling precise bioconjugation with diverse functional groups.

Macrocyclic phage display for identification of selective protease substrates

This paper introduces a method using macrocyclic phage display to identify selective protease substrates, demonstrating its effectiveness with FAP and DPP4.

Influence of Macrocyclization Strategies on DNA-Encoded Cyclic Peptide Libraries

This study evaluates how different macrocyclization strategies affect DNA-encoded cyclic peptide library selections against MDM2 and GIT1, identifying potent inhibitors and elucidating binding mechanisms.

Screening macrocyclic peptide libraries by yeast display allows control of selection process and affinity ranking

This paper develops a yeast display method to screen macrocyclic peptide libraries, enabling better selection and affinity ranking of ligands against diverse protein targets.

Accurate de novo design of high-affinity protein binding macrocycles using deep learning

This paper introduces RFpeptides, a deep learning framework for designing high-affinity macrocyclic peptides, achieving sub-nanomolar binding affinities and accurate structural predictions.

Defining short linear motif binding determinants by phage-based multiplexed deep mutational scanning

This study uses phage-based deep mutational scanning to identify binding determinants of short linear motifs between human and SARS-CoV-2 proteins, refining motifs and identifying affinity-enhancing mutations.

An mRNA Display Approach for Covalent Targeting of a Staphylococcus aureus Virulence Factor

The paper develops fluorescent probes for FphB, a Staphylococcus aureus enzyme, using mRNA display with a genetically encoded electrophile, achieving nanomolar selectivity.

Identification of Covalent Cyclic Peptide Inhibitors Targeting Protein-Protein Interactions Using Phage Display

This paper identifies covalent cyclic peptide inhibitors targeting protein-protein interactions using phage display, demonstrating antiviral activity against SARS-CoV-2.

Exploring the effect of Hydrocarbon Cross-linkers on the Structure and Binding of Stapled p53 Peptides

This study uses simulations to analyze how hydrocarbon cross-linkers affect the structure and binding of stapled p53 peptides to MDM2, showing that longer cross-linkers increase rigidity and improve binding efficiency.

Enzyme-free biochemical production of seamlessly N-to-C cyclized peptides from natural or recombinant proteins

This paper describes a method to produce cyclic peptides from natural or recombinant proteins without enzymes, enabling cost-effective and scalable synthesis of stable, biodegradable cyclic peptides.