Chemical Synthesis and Analysis

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.

Structure-guided generative design of peptides targeting the FtsQBL divisome complex inhibit Escherichia coli cell division.

This study designs peptides targeting the FtsQBL divisome complex in E. coli using structure-guided methods, showing they inhibit cell division.

BOND-PEP: topology-conditioned bipartite alignment for evidence-grounded peptide binder generation

BOND-PEP generates controllable peptide binders using topology-conditioned bipartite alignment and retrieval-augmented methods, achieving state-of-the-art results with sequence-only inputs.

Universal Baseline for in vitro Selection of Genetically Encoded Libraries

The paper introduces a universal baseline method to improve reproducibility in in vitro selection of genetically encoded libraries using NGS data.

Synthesis based on covalent capture and release (SCCR): a programmable strategy for automated preparation of protease-activatable molecules

This paper introduces a programmable chemical strategy called SCCR for automated synthesis of protease-activatable molecules, demonstrating its application in generating fluorogenic probes and ADC linkers.

A Novel Method for Normalizing Data from DNA-Encoded Library Selections

The paper introduces a normalization method for DNA-encoded library selections using antibody fragments and DNA-conjugated peptides to improve accuracy and reduce noise in data analysis.

Intracellular Bismuth Coordination of Peptides and Miniproteins

This paper demonstrates intracellular bismuth-mediated cyclisation of peptides and miniproteins in E. coli, producing stable structures with minimal toxicity.

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.

Evaluation of peptidomimetic inhibitors

The paper evaluates peptidomimetic inhibitors using a set of complementary assays to support drug discovery.

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.

Mapping the diverse topologies of protein-protein interaction fitness landscapes

The paper identifies target-specific fitness landscapes in protein-protein interactions and develops a supervised contrastive learning approach to predict binders.

Atom-level backbone engineering preserves peptide function while enhancing stability

This study evaluates four peptide backbone modifications to enhance stability while preserving function, finding that azapeptides maintain activity and offer improved stability.

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.

Model Agnostic Conditioning of Boltzmann Generators for Peptide Cyclization

This paper introduces a model-agnostic framework to condition Boltzmann generators for sampling cyclic peptide conformations without retraining, using chemically informed loss functions and geometric constraints.

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.

Generative Design of High-Affinity Peptides Using BindCraft

This study uses BindCraft to design high-affinity peptides for protein targets, achieving nanomolar affinities for some targets and improving potency through stapling.

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.

Blind De Novo Design of Dual Cyclic Peptide Agonists Targeting GCGR and GLP1R

This paper designs cyclic peptide agonists for GCGR and GLP1R using EvoBind, achieving dual activation with EC50 values comparable to natural hormones.