Biology subjects

Bera, A. K.

Publications and source records attributed to Bera, A. K..

At least 19 recordsLinked to original sources

bioRxiv2026

Design of readers for pathological PTM proteoforms in Alzheimer's disease

Alzheimer's disease (AD) is characterized by heterogeneous Tau phosphorylation and aberrant amyloid-beta (Abeta) processing, yet molecular tools that distinguish closely related molecular states of tau and Abeta with predefined specificity remain difficult to develop. Here, we designed de novo protein readers targeting three disease-associated phospho-Tau regions and N-terminal pyroglutamate-modified Abeta (N3pG-Abeta). Screening 192 designs per target identified 51 modification-selective hits among 768 candidates (6.6%). Representative readers exhibited nanomolar to subnanomolar affinities for modified peptides, discriminated authentic modifications from unmodified or substitution-based controls, and preferentially recognized modified full-length targets. We further programmed local modification specificity by interface redesign, generating pT231 readers conditional on the phosphorylation state of neighboring S235 and S237. A 2.0-angstrom crystal structure of an N3pG-Abeta reader closely matched the computational design model (interface C-alpha RMSD = 0.52 angstrom), and redesign of pT231 readers tuned apparent binding affinities from greater than 1 uM to below 1 nM. In a human 3D neuronal culture with both pathological Abeta and tau, selective readers targeting N3pG-Abeta, Tau pT231, and Tau pT217 recognized disease-associated signals, exhibiting colocalization with related antibodies and much higher signal in the AD line than the control. Tau pT231 readers further quantitatively distinguish AD patients and control human brain lysates in dot-blot assays. Together, these results establish genetically encoded readers with programmable specificity for defined Tau and Abeta modification states, enabling molecular-state-resolved detection in human disease models and biological samples, and lay a foundation for controlled pathological molecular perturbation.

bioengineering↗

bioRxiv2026

Lactate Promotes Tunneling Nanotube Formation and Reduces Temozolomide Sensitivity in Glioblastoma Cells

Tunneling nanotubes (TNTs) mediate intercellular communication and contribute to cancer progression. Tumour cells produce excess lactate through increased glycolysis, but whether lactate regulates TNT formation has not been studied. Here, we show that lactate promotes TNT formation in U-87 MG glioblastoma (GBM) cells under both glucose-restricted and glucose-replete conditions, with a similar effect in MDA-MB-231 breast cancer cells. This effect depends on lactate uptake and metabolism rather than receptor-mediated signalling: inhibition of monocarboxylate transporter 1 (MCT1) or lactate dehydrogenase (LDH) reduced TNT formation, while exogenous lactate restored TNT formation during LDH inhibition. 3-chloro-5-hydroxybenzoic acid, an agonist of the plasma membrane-localized lactate receptor (GPR81/HCAR1), did not reproduce the effect of lactate. Lactate also increased intercellular mitochondrial transfer, attenuated temozolomide (TMZ)-induced growth suppression of GBM spheroids, and increased expression of the TNT-associated genes CDC42, MYO10 and FSCN1. Inhibition of p300/CBP-mediated lactylation with A-485 reduced both protein lactylation and TNT formation, implicating lactylation in TNT biogenesis. Lactate increased basal and ATP-linked respiration that persisted during MCT1 inhibition and reduced on LDH inhibition, indicating that the effects of lactate on respiration and on TNT formation are at least partly separable. Together, these findings identify lactate as a regulator of TNT formation and link tumour metabolism to intercellular connectivity and TMZ response, highlighting lactate metabolism and lactylation as potential therapeutic targets.

cell biology↗

bioRxiv2026

De novo design of allosterically controlled enzymes

The ability of enzymes to sense signals and respond by changing their structure and activity underlies cellular processes from signaling to metabolic control. While there have been recent advances in the de novo design of enzymes and conformationally switching proteins, combining these to achieve allosteric regulation of enzymatic activity in a fully designed system remains an outstanding challenge. Here, we show that denoising diffusion models enable the design of compact de novo enzymes whose activity can be allosterically activated or repressed by designed protein effectors. Our results establish a general route to allosteric control over a wide range of catalytic and other protein functions.

biochemistry↗

bioRxiv2026

Programmable De Novo Design of Mesoporous Protein Crystal Frameworks

Three-dimensional protein crystals are ordered, porous macroscopic materials with potential applications in catalysis, biosensing, and biomedicine. However, most protein crystals are obtained by empirical screening, providing limited control over the lattice architecture, pore geometry or component composition that determine material function. Here, we present a modular strategy for the programmable design of highly porous, framework-like protein crystals using predefined protein-protein interactions. This strategy yielded over 30 distinct protein crystals, including single-component and multicomponent P213 and I213 lattices that grow to over 100 micrometers in size. Small-angle X-ray scattering and electron microscopy showed close agreement between experimental lattices and computational models. RFdiffusion-guided design generated isomorphous variants with matched lattice parameters, enabling coherent protein crystal alloys, epitaxial core-shell growth and reversible shell assembly. The designed crystals exhibit tunable mesoporous architectures, with limiting apertures of 2-18 nm, and support genetically encoded incorporation of fluorescent protein guests. These results establish a general route to programmable lattice engineering of protein crystals and position them as genetically encoded, compositionally tunable mesoporous materials.

synthetic biology↗

bioRxiv2026

De novo design of autocatalytically forming intra- and intermolecular isopeptide bonds to construct rigid covalent protein assemblies

Isopeptide bonds are amide bonds between amino acid side chains that can form autocatalytically, notably in the pili of Gram-positive bacteria. Here, we design de novo proteins that form both intramolecular and intermolecular isopeptide bonds entirely autocatalytically. We report over 50 designs that form isopeptide bonds, validated by mass spectrometry and 5 crystal structures. We redesign these constructs as split proteins that form a covalent intermolecular isopeptide crosslink when combined. These split designs are orthogonal to the existing isopeptide-based SpyTag/Catcher system, and their formation can be regulated by temperature, providing control over the timing of crosslinking in protein assemblies. We extend these designs to create rigid domain crosslinks that enable the construction of large well ordered symmetric rings of up to 215 kDa that are irreversibly covalently crosslinked by multiple isopeptide bonds into a single molecule. Our results provide insight into the determinants of isopeptide bond formation, considerably expand the set of isopeptide bond crosslinking systems, and establish a framework to construct fully covalent rigid protein assemblies.

biophysics↗

bioRxiv2026

Altered volume-regulated anion channel activity contributes to depression and anxiety-related molecular and behavioural phenotypes in zebrafish

Major depressive disorder (MDD) is a leading cause of global morbidity and mortality. Unfortunately, a substantial proportion of patients do not respond adequately to currently available therapies, highlighting the need for new therapeutic targets. Here, we investigated the role of volume-regulated anion channel (VRAC) in depression-related phenotypes using zebrafish. Disruption of VRAC function, either by pharmacological inhibition or morpholino-mediated knockdown of lrrc8aa, the zebrafish ortholog of mammalian LRRC8A, the obligatory subunit required for VRAC function, induced anxiety- and depression-like behaviours in zebrafish larvae and altered the expression of genes associated with affective disorders. Transcriptomic analysis of lrrc8aa-deficient larvae revealed dysregulation of pathways involved in neuronal signalling and cellular stress responses. Conversely, pharmacological activation of VRAC with zinc pyrithione (ZPT) improved behavioural abnormalities and partially restored altered gene expression. In adult zebrafish subjected to chronic unpredictable stress, ZPT produced antidepressant- and anxiolytic-like effects comparable to those of imipramine and normalized elevated monoamine oxidase (mao) expression. Together, these findings indicate that reduced VRAC function contributes to depression- and anxiety-related behavioural and molecular phenotypes and identify VRAC as a potential target for the development of novel antidepressant therapies. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=149 SRC="FIGDIR/small/740018v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@d81884org.highwire.dtl.DTLVardef@131b8e9org.highwire.dtl.DTLVardef@162d1d0org.highwire.dtl.DTLVardef@bcdb82_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2026

Orally available designed miniproteins inhibit enterotoxigenic Bacteroides fragilis pathology by blocking toxin receptor binding

Toxigenic bacterial infections in the gut are a significant contributor to the global burden of disease. Advanced tools for protein and live biotherapeutic engineering offer potentially transformative strategies for treating such diseases, while avoiding the collateral effects of traditional antibacterials. Here we used de novo protein design to identify inhibitors of the metzincin family protease Bacteroides fragilis toxin (BFT). These inhibitors, which bind distal to the active site, interfere with toxin-mediated E-cadherin cleavage and downstream proinflammatory signaling by blocking claudin-4 receptor binding. We tested the inhibitors as disulfide-stabilized variants administered directly to the cecum or in drinking water, as well as through in situ secretion by an engineered live biotherapeutic. Across these delivery modalities, the inhibitors successfully neutralized the toxin and effectively prevented BFT-associated gut pathology, including tumor formation. These results highlight the potential of de novo designed proteins as precise, non-antibiotic interventions to mitigate bacterial toxin-driven disease in the gut.

microbiology↗

bioRxiv2026

Controlling metal-carbonate phase, form, and function through de novo protein design

Biomineralization enables living systems to construct hybrid materials by controlling the location, orientation, and polymorph of inorganic crystals with proteins and other biomolecules. Despite decades of study, the molecular principles underlying these processes remain difficult to harness in engineered materials, in part because native biomineralization proteins are often intrinsically disordered, heterogeneous, or insoluble. Here we show that de novo designed protein interfaces can be assembled into reconfigurable two-dimensional arrays which template calcite nanocrystals. By fine-tuning RFdiffusion2 on repeat protein scaffolds, we further enable the design of protein architectures which selectively form aragonite, a metastable polymorph of calcium carbonate, in nucleation conditions that otherwise result in a mixture of phases. Extending beyond inorganics found in biological systems, we show that lattice-matched protein designs template cobalt carbonate formation: a flat helical repeat protein interface promotes unconfined growth, whereas soluble D3 cage assemblies yield more homogenous cobalt carbonate nanocrystals confined to the interior of the cage. These protein-cage cobalt carbonate hybrid materials function as electrocatalysts for alkaline water splitting. Our results demonstrate the potential of deep learning-based methods to unlock the structural and functional activity of protein-mineral composites.

biochemistry↗

bioRxiv2026

Computational design of membrane fusion proteins

The fusion of two distinct biological membranes is an evolutionarily conserved process essential to cellular organization and physiology. Membrane fusion is driven by the refolding of fusogenic proteins into low-energy postfusion states that overcome the energetic barrier to bilayer merger. Here we report a computational method for the design of synthetic fusogens inspired by the architecture of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. Using machine learning-guided protein design to extensively remodel backbone geometry and sequence, we generated heterodimeric SNARE-like assemblies that efficiently catalyze cell-cell membrane fusion. These minimal two-component fusogens exhibit substantially higher fusion activity than native multisubunit SNARE complexes. Structural and functional analyses identify the key determinants required for fusogenic activity and reveal a modularity that enables control of fusion through chemically induced heterodimerization. In addition to cell-cell fusion, the synthetic fusogens drive fusion between endoplasmic reticulum and mitochondrial membranes from human cells, demonstrating their potential as tools for programmable manipulation of intracellular membranes. Together, these results establish a general framework for the rational design of synthetic fusogens and expand the toolkit for engineering membrane dynamics in living systems.

biochemistry↗

bioRxiv2026

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

Investigating and manipulating cellular events requires precise control of protein function. To enable control over cellular processes, we set out to design a chemically induced dimerization (CID) system consisting of a de novo designed ligand and protein pair. Here we describe the design of a C2 symmetric membrane permeable macrocyclic peptide and a cognate protein homodimer which binds the macrocycle through a large interface with both chains. The designed homodimer binds the macrocycle with a KD of 36 nM, and the x-ray crystal structure of the protein homodimer-macrocycle complex is very close to the computational design model, with the C2 axis of the macrocycle aligned with the homodimer C2 axis. Transcriptional and split luciferase assays in mammalian cells demonstrates conditional control over both a reporter gene expression and luciferase reconstitution.

biochemistry↗

bioRxiv2026

A neuropsychiatric disease-associated mutation in LRRC8B disrupts cellular calcium signaling, mitochondrial function, and bioenergetics

Leucine-rich repeat-containing 8 (LRRC8) proteins form the volume-regulated anion channel (VRAC) and participate in diverse physiological processes, including cell volume regulation, gliotransmitter release, and insulin secretion. In mammals, five paralogs (LRRC8A-E) exist; LRRC8A is the obligatory subunit that assembles into functional hexameric channels with LRRC8C, D, or E. LRRC8B is distinct: we previously demonstrated its role in regulating endoplasmic reticulum (ER) Ca{superscript 2} homeostasis and ER Ca{superscript 2} leak. A LRRC8B variant (Y380S) identified in an Indian family with severe mental illness has been associated with disease pathology, but its molecular and cellular consequences remain unknown. Here, we show that this disease-associated mutant perturbs Ca{superscript 2} signalling, mitochondrial bioenergetics, and redox homeostasis. Both wild-type and mutant LRRC8B localize to the ER and mitochondria. LRRC8B knockdown significantly reduced mitochondrial Ca{superscript 2} uptake and maximal respiratory the Y380S mutant phenocopied LRRC8B knockdown, altering ER Ca{superscript 2} release, elevating basal cytosolic Ca{superscript 2}, and impairing mitochondrial Ca{superscript 2} uptake, consistent with a dominant-negative mechanism. The mutant further induced mitochondrial dysfunction, including loss of membrane potential, oxidative stress, and defective antioxidant responses, ultimately compromising cellular bioenergetics and viability. Mechanistically, the Y380S mutation disrupted LRRC8B interaction with the mitochondrial outer membrane channel VDAC. These findings identify LRRC8B-VDAC coupling as a key determinant of mitochondrial Ca{superscript 2} handling and provide a mechanistic link between LRRC8B dysfunction and neuropsychiatric disease. HighlightsO_LIA psychiatric disease-associated LRRC8B variant (Y380S) acts as a dominant-negative regulator of ER Ca{superscript 2} homeostasis. It enlarges the releasable ER Ca{superscript 2} pool and reduces cell viability. C_LIO_LILRRC8B promotes mitochondrial Ca{superscript 2} uptake through interaction with VDAC. The Y380S mutation disrupts this interaction, reducing mitochondrial Ca{superscript 2} uptake. C_LIO_LIThe Y380S mutant increases mitochondrial superoxide production without activating compensatory antioxidant responses. C_LIO_LIThe mutant also causes mitochondrial membrane depolarization and bioenergetic failure, as evidenced by reduced oxygen consumption rate and ATP production. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/718892v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@1f314d3org.highwire.dtl.DTLVardef@1dc3908org.highwire.dtl.DTLVardef@124445aorg.highwire.dtl.DTLVardef@39326_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2026

PIGBOS-CLCC1 Interaction Shapes Cellular Calcium Dynamics and Energy Metabolism

PIGBOS is a recently identified 54-amino acid microprotein localized to the mitochondrial outer membrane and implicated in the endoplasmic reticulum (ER) stress response. Here, we identify a previously unrecognized role for PIGBOS in cellular Ca2+ homeostasis. Manipulation of PIGBOS expression in HEK293T cells revealed that PIGBOS enhances Ca2+ signaling by promoting ER Ca2+ release through inositol 1,4,5-trisphosphate (IP3) receptors and subsequent mitochondrial Ca2+ uptake in response to histamine stimulation. In contrast, siRNA-mediated depletion or genetic ablation of PIGBOS markedly attenuated these responses. PIGBOS selectively facilitated Ca2+ transfer from the ER to mitochondria without affecting mitochondrial Ca2+ uptake from non-ER sources and also promoted store-operated Ca2+ entry. Functional analyses demonstrated that the interaction of PIGBOS with the ER-resident chloride channel CLCC1 via its C-terminal region is required for this activity. Network analysis predicted a direct association between PIGBOS and CLCC1, as well as indirect connections with core Ca2+ signaling components, including IP3 receptors, STIM1, Orai1, and SERCA, whose expression was altered upon modulation of PIGBOS abundance. Loss of PIGBOS impaired mitochondrial respiration, reduced ATP production, and increased reactive oxygen species. Together, these findings establish PIGBOS as a key regulator of ER-mitochondrial Ca2+ signaling that couples Ca2+ dynamics to mitochondrial bioenergetics and cellular stress responses. Significance StatementThis study identifies PIGBOS, a mitochondrial microprotein, as a key regulator of cellular Ca2+ signaling through its interaction with the endoplasmic reticulum (ER) chloride channel CLCC1. By coordinating ER-mitochondrial Ca2+ transfer and modulating the expression of key Ca2+ signaling-associated proteins, PIGBOS integrates cellular Ca2+ dynamics with mitochondrial energy metabolism and stress responses. Given that perturbations in Ca2+ homeostasis profoundly influence cell survival and energy production, these findings reveal a new paradigm of inter-organelle communication. This work has broad implications for understanding the molecular basis of disorders such as neurodegeneration and cancer, where Ca2+ signaling and homeostasis are disrupted.

cell biology↗

bioRxiv2025

Computational design of cysteine proteases

Despite advances in de novo enzyme design, success has been largely limited to low energy barrier model reactions. Amide bonds such as those linking amino acids along the peptide backbone are stable for hundreds of years in neutral aqueous solution because of the high energy barrier to hydrolysis. Here we describe the de novo design of enzymes which utilize an activated cysteine nucleophile to hydrolyze the polypeptide backbone in a sequence-dependent manner, with a success rate of 13/69=19% and rate enhancements over the background reaction (kcat/kuncat) of up to 3 x 10^7. The designed proteases have folds very different from proteases in nature (TM score < 0.50), and six crystal structures are very close to the design models (Ca RMSDs < 1.2 A), highlighting the capacity for generalization and the accuracy of the design methodology. Experimental and computational analyses suggest that the remaining gap in activity to the most active native cysteine proteases arises from imperfections in active site preorganization and substrate positioning. The designed proteases efficiently cleave their targets in mammalian cells, opening the door to a wide range of synthetic biology applications.

biochemistry↗

bioRxiv2025

De novo design of phospho-tyrosine peptide binders

Phosphorylation on tyrosine is a key step in many signaling pathways. Despite recent progress in de novo design of protein binders, there are no current methods for designing binders that recognize phosphorylated proteins and peptides; this is a challenging problem as phosphate groups are highly charged, and phosphorylation often occurs within unstructured regions. Here we introduce RoseTTAFold Diffusion 2 for Molecular Interfaces (RFD2-MI), a deep generative framework for the design of binders for protein, ligand, and covalently modified protein targets. We demonstrate the power and versatility of this method by designing binders for four critical phosphotyrosine sites on three clinically relevant targets: Cluster of Differentiation 3 (CD3{varepsilon}), Epidermal Growth Factor Receptor (EGFR), Insulin Receptor (INSR) and Signal Transducer and Activator of Transcription 5 (STAT5). Experimental characterization shows that the designs bind their phosphotyrosine containing targets with affinities comparable to native binding sites and have negligible binding to non-phosphorylated targets or phosphopeptides with different sequences. X-ray crystal structures of generated binders to CD3{varepsilon} and EGFR are very close to the design models, demonstrating the accuracy of the design approach. A designed binder to an EGFR intracellular region phosphorylated upon EGF activation co-localizes with the receptor following EGF stimulation in single-particle tracking (SPT) experiments, demonstrating pY specific recognition in living cells. RFD2-MI provides a generalizable all-atom diffusion framework for probing and modulating phosphorylation-dependent signaling, and more generally, for developing research tools and targeted therapeutics against post-translationally modified proteins.

bioengineering↗

bioRxiv2025

De Novo Design of Miniprotein Inhibitors of Bacterial Adhesins

The rise of multidrug-resistant bacterial infections necessitates the discovery of novel antimicrobial strategies. Here, we show that protein design provides a generalizable means of generating new antimicrobials by neutralizing the function of bacterial adhesins, which are virulence factors critical in host-pathogen interactions. We de novo designed high-affinity miniprotein binders to FimH and Abp chaperone usher pili adhesins from uropathogenic Escherichia coli and Acinetobacter baumannii, respectively, which are implicated in mediating both uncomplicated and catheter-associated urinary tract infections (UTI) responsible for significant morbidity worldwide. The designed antagonists have high specificity and stability, disrupt bacterial recognition of host receptors, block biofilm formation, and are effective in treating and preventing murine models of uncomplicated and catheter- associated UTIs in vivo.

microbiology↗

bioRxiv2025

Design of Orthogonal Far-Red, Orange and Green Fluorophore-binding Proteins for Multiplex Imaging

Fluorescent proteins and small molecule dyes have complementary strengths for biological imaging: the former are genetically manipulatable enabling tagging of specific proteins and detection of protein interactions, while the latter have greater photostability and brightness but are difficult to target. To combine these strengths, we used de novo protein design to generate binders to three bright, stable, cell-permeable dyes spanning the visible spectrum: JF657 (far red), JF596 (orange-red) and JF494 (green). For each dye, we obtain nanomolar binders with weak or no binding to the other two dyes; the accuracy of the design approach is confirmed by a crystal structure of one binder which is very close to the design model. Fusion of the JF567, JF596 and JF494 binders to three different targets followed by staining with the three dyes simultaneously enables multiplex imaging. We further expand functionality by incorporating an active site carrying out nucleophilic aromatic substitution to form a covalent linkage with the dye, and developing split versions which reconstitute fluorescence at subcellular locations where both halves are present, enabling both protein-protein interaction detection and chemically induced dimerization with fluorescence reporting. Our designs combine the advantages of fluorescent proteins and small molecule dyes and should be broadly useful for cellular imaging.

biochemistry↗

bioRxiv2025

Designed NGF mimetics with reduced nociceptive signatures in neurons

The clinical use of Nerve Growth Factor (NGF) for neuronal regeneration has been hampered by pain sensitization side effects. NGF signals through the receptor tyrosine kinase TrkA and the co-receptor p75NTR; pain sensitization is thought to involve p75NTR. We sought to overcome this limitation by de novo design of a TrkA agonist that does not bind p75NTR. We designed homodimeric TrkA engaging constructs that dimerize TrkA subunits in a variety of geometries, and identified those eliciting the strongest signaling. The resulting designed agonists are able to stimulate transdifferentiated neurons and neuroblastoma cell lines, leading to neurite outgrowth and neuronal differentiation, with considerably reduced transcription of inflammation and pain related genes. These agonists are promising candidates for promoting neuronal regeneration without adverse side effects. HighlightsO_LIDe novo designed TrkA agonists activate MAPK and PI3K-AKT signaling C_LIO_LIRigid fusions allow for highly tunable signaling signatures C_LIO_LITrkA agonists lead to neurite outgrowth in neuroblastoma cells comparable to retinoic acid C_LIO_LIModulation of the TrkA pathway without co-stimulating p75NTR leads to a downregulation of inflammatory and nociceptive signature in neurons. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/648806v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@c48066org.highwire.dtl.DTLVardef@c9c5a7org.highwire.dtl.DTLVardef@cf8ebdorg.highwire.dtl.DTLVardef@a4345a_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2024

Design of facilitated dissociation enables control over cytokine signaling duration

Protein design has focused primarily on the design of ground states, ensuring they are sufficiently low energy to be highly populated1. Designing the kinetics and dynamics of a system requires, in addition, the design of excited states that are traversed in transitions from one low-lying state to another2,3. This is a challenging task as such states must be sufficiently strained to be poorly populated, but not so strained that they are not populated at all, and because protein design methods have generally focused on creating near-ideal structures4-7. Here we describe a general approach for designing systems which use an induced-fit power stroke8 to generate a structurally frustrated9 and strained excited state, allosterically driving protein complex dissociation. X-ray crystallography, double electron-electron resonance spectroscopy, and kinetic binding measurements demonstrate that incorporating excited states enables design of effector-induced increases in dissociation rates as high as 6000-fold. We highlight the power of this approach by designing cytokine mimics which can be dissociated within seconds from their receptors.

biochemistry↗