Charged Moieties Research Articles

High-performance portable graphene field-effect transistor device for detecting Gram-positive and -negative bacteria

Current techniques for Gram-typing and for diagnosing a pathogen at the early infection stage rely on Gram stains, cultures, Enzyme linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), and gene microarrays, which are labor-intensive and time-consuming approaches. In addition, a delayed or imprecise diagnosis of clinical pathogenic bacteria leads to a life-threatening emergency or overuse of antibiotics and a high-rate occurrence of antimicrobial-resistance microbes. Herein, we report high-performance antibiotics (as bioprobes) conjugated graphene micropattern field-effect transistors (ABX-GMFETs) to facilitate on-site Gram-typing and help in the detection of the presence or absence of Gram-negative and -positive bacteria in the samples. The ABX-GMFET platform, which consists of recognition probes and GM transistors conjugated with novel interfacing chemical compounds, was integrated into the microfluidics to minimize the required human intervention and facilitate automation. The mechanism of binding of ABX-GMFET was based on a charge or chemical moiety interaction between the bioprobes and target bacteria. Subsequently, ABX-GMFETs exhibited unprecedented high sensitivity with a limit of detection (LOD) of 100 CFU/mL (1–9 CFU/mL), real-time target specificity.

A practical guide to biologically relevant molecular simulations with charge scaling for electronic polarization.

Molecular simulations can elucidate atomistic-level mechanisms of key biological processes, which are often hardly accessible to experiment. However, the results of the simulations can only be as trustworthy as the underlying simulation model. In many of these processes, interactions between charged moieties play a critical role. Current empirical force fields tend to overestimate such interactions, often in a dramatic way, when polyvalent ions are involved. The source of this shortcoming is the missing electronic polarization in these models. Given the importance of such biomolecular systems, there is great interest in fixing this deficiency in a computationally inexpensive way without employing explicitly polarizable force fields. Here, we review the electronic continuum correction approach, which accounts for electronic polarization in a mean-field way, focusing on its charge scaling variant. We show that by pragmatically scaling only the charged molecular groups, we qualitatively improve the charge-charge interactions without extra computational costs and benefit from decades of force field development on biomolecular force fields.

Hydrophilic Microporous Polymer Membranes: Synthesis and Applications.

Ion and water transfer in subnanometer-sized confined channels of hydrophilic microporous polymer membranes show enormous potential in tackling the ubiquitous trade-off between permeability and selectivity for energy and environment-related membrane technologies. To this end, a variety of hydrophilic polymers of intrinsic microporosity (HPIMs) have been developed. Herein, the synthetic strategies toward HPIMs are summarized, including post-synthetic modification of polymers to introduce polar groups (e. g., amines, hydroxy groups, carboxylic acids, tetrazoles) or charged moieties (e. g., quaternary ammonium salts, sulfonic acids), and the polymerization of hydrophilic monomers. The advantages of HPIM membranes over others when employed in energy conversion and storage, acid gas capture and separation, ionic diodes, and ultrafiltration, are highlighted.

Polymers in the Medical Antiviral Front-Line.

Antiviral polymers are part of a major campaign led by the scientific community in recent years. Facing this most demanding of campaigns, two main approaches have been undertaken by scientists. First, the classic approach involves the development of relatively small molecules having antiviral properties to serve as drugs. The other approach involves searching for polymers with antiviral properties to be used as prescription medications or viral spread prevention measures. This second approach took two distinct directions. The first, using polymers as antiviral drug-delivery systems, taking advantage of their biodegradable properties. The second, using polymers with antiviral properties for on-contact virus elimination, which will be the focus of this review. Anti-viral polymers are obtained by either the addition of small antiviral molecules (such as metal ions) to obtain ion-containing polymers with antiviral properties or the use of polymers composed of an organic backbone and electrically charged moieties like polyanions, such as carboxylate containing polymers, or polycations such as quaternary ammonium containing polymers. Other approaches include moieties hybridized by sulphates, carboxylic acids, or amines and/or combining repeating units with a similar chemical structure to common antiviral drugs. Furthermore, elevated temperatures appear to increase the anti-viral effect of ions and other functional moieties.

Novel choline selective electrochemical membrane sensor with application in milk powders and infant formulas

Choline (Ch+), is a vitamin-like essential water-soluble organic micronutrient. The US-FDA requires that infant formula not made from cow's milk must be supplemented with Ch+. Direct determination of Ch+ in milk powders and infant formulas is a challenging task due to the lack of a detectable chromophore, its existence in free and complexed forms as well as the presence of multi-analytes in these complex matrices. Here, an enzyme-free potentiometric ion selective electrode (ISE) with high selectivity for Ch+, a linear range from 0.03 μM up to 1 mM, a 0.061 μM detection limit (LOD) and a typical response time less than 5 and no greater than 60 s is developed for monitoring of Ch+ in infant formula and milk powders. To achieve these ISE parameters we relied on the ability of calixarenes and its derivatives to form host-guest complexes with the positively charged quaternary ammonium moiety of Ch+. We employed a lipophilic (membrane-compatible) calixarene as an ionophore in the sensing membrane phase to provide a molecular receptor for Ch+ capable of selective binding; while utilizing, hydrophilic (water-soluble) p-sulfonated calixarene as a buffering agent to optimize the inner filling solution to reduce transmembrane Ch+ fluxes. All the calixarene structures and their complexes with Ch+ were optimized at the density functional theory (DFT) level and the Gibbs free energies for the inclusion of Ch+ into the calixarenes were calculated. The prepared sensor was shown to selectively respond only to Ch+ in the presence of all other interferents in the tested matrices with results that are not statistically significantly different for either accuracy or precision relative to the much more laborious official AOAC 1999 coupled enzymatic–spectrophotometric method. The proposed method is highly selective, non-enzymatic, requires no derivatization or incubation steps, offers a fast response time, and has the potential of portability for in situ analysis, while being relatively cost effective and non-laborious.

A nanotrap improves survival in severe sepsis by attenuating hyperinflammation

Targeting single mediators has failed to reduce the mortality of sepsis. We developed a telodendrimer (TD) nanotrap (NT) to capture various biomolecules via multivalent, hybrid and synergistic interactions. Here, we report that the immobilization of TD-NTs in size-exclusive hydrogel resins simultaneously adsorbs septic molecules, e.g. lipopolysaccharides (LPS), cytokines and damage- or pathogen-associated molecular patterns (DAMPs/PAMPs) from blood with high efficiency (92–99%). Distinct surface charges displayed on the majority of pro-inflammatory cytokines (negative) and anti-inflammatory cytokines (positive) allow for the selective capture via TD NTs with different charge moieties. The efficacy of NT therapies in murine sepsis is both time-dependent and charge-dependent. The combination of the optimized NT therapy with a moderate antibiotic treatment results in a 100% survival in severe septic mice by controlling both infection and hyperinflammation, whereas survival are only 50–60% with the individual therapies. Cytokine analysis, inflammatory gene activation and tissue histopathology strongly support the survival benefits of treatments.

An Aminopyridinium Ionic Liquid: A Simple and Effective Bifunctional Organocatalyst for Carbonate Synthesis from Carbon Dioxide and Epoxides.

An aminopyridinium ionic liquid is presented as a green, tunable, and active metal-free one-component catalytic system for the atom-efficient transformation of oxiranes and CO2 to cyclic carbonates. Inclusion of a positively charged moiety into aminopyridines, through a simple single-step synthesis, provides a one-component ionic liquid catalytic system with superior activity; effective in ring opening of epoxide, CO2 inclusion, and stabilization of oxoanionic intermediates. An efficiency assessment of a variety of positively charged aminopyridines was pursued, and the impact of temperature, catalyst loading, and the kind of nucleophile on the catalytic performance was also investigated. Under solvent-free conditions, this bifunctional organocatalytic system was used for the preparation of 18 examples of cyclic carbonates from a broad range of alkyl- and aryl-substituted oxiranes and CO2 , where up to 98 % yield and high selectivity were achieved. DFT calculations validated a mechanism in which nucleophilic ring-opening and CO2 inclusion occur simultaneously towards cyclic carbonate formation.

Antimicrobial Peptides as Anticancer Agents: Functional Properties and Biological Activities.

Antimicrobial peptides (AMPs), or host defense peptides, are small cationic or amphipathic molecules produced by prokaryotic and eukaryotic organisms that play a key role in the innate immune defense against viruses, bacteria and fungi. AMPs have either antimicrobial or anticancer activities. Indeed, cationic AMPs are able to disrupt microbial cell membranes by interacting with negatively charged phospholipids. Moreover, several peptides are capable to trigger cytotoxicity of human cancer cells by binding to negatively charged phosphatidylserine moieties which are selectively exposed on the outer surface of cancer cell plasma membranes. In addition, some AMPs, such as LTX-315, have shown to induce release of tumor antigens and potent damage associated molecular patterns by causing alterations in the intracellular organelles of cancer cells. Given the recognized medical need of novel anticancer drugs, AMPs could represent a potential source of effective therapeutic agents, either alone or in combination with other small molecules, in oncology. In this review we summarize and describe the properties and the mode of action of AMPs as well as the strategies to increase their selectivity toward specific cancer cells.

Poly(vinyl chloride)-hyperbranched polyamidoamine ultrafiltration membranes with antifouling and antibiofouling properties

Poly(vinyl chloride) (PVC) ultrafiltration membranes with improved antifouling and antibiofouling properties were prepared by non-solvent induced phase inversion using a hyperbranched polyamidoamine as additive. PVC reacted into the casting solution with the commercial polyamidoamine nanomaterial Helux-3316 by means of a nucleophilic substitution reaction. The composition of neat and functionalized membranes was studied by ATR-FTIR and elemental composition. Amino groups were tracked using the fluorescent dye fluorescamine. Surface ζ-potential and water contact angles were used to measure surface charge and hydrophilicity of tested membranes. The incorporation of amino groups increased membrane hydrophilicity and surface porosity, which resulted in enhanced permeability. Functionalized membranes displayed antifouling behaviour revealed upon filtering BSA solutions and lower irreversible fouling than PVC membranes. The attachment of Helux moieties to PVC yielded membranes with antibiofouling functionality explained by the interaction of positively charged Helux moieties with the negatively charged cell envelopes. Growth reduction for cells attached to the membrane surface during filtration reached up to 1-log for the Gram-positive bacterium S. aureus. This investigation revealed that the incorporation of the hyperbranched nanomaterial in concentrations in the order of 1 wt% in the casting solution provides significant benefits to membrane performance, in terms of permeability and antifouling potential.

Controlled Synthesis of Gold Nanoparticles in Copolymers Nanomolds by X-ray Radiolysis.

We show by X-ray and neutron small-angle scattering that gold nanoparticles with controlled sizes and morphologies can be obtained by the metallic reduction of AuCl4- ions trapped in 3D organic molds by X-ray radiolysis. The molds are spherical frozen micelles of polystyrene-b-poly(dimethylaminoethyl methacrylate) (PS-b-PDMAEMA) block copolymer in acidic aqueous solution with a PS spherical core surrounded by a corona of PDMAEMA chains in good solvent. The behavior of micelles is controlled by the [AuCl4-]/[DMAEMA] ratio RAuCl4-/DMAEMA. At low gold concentration, AuCl4- ions condense on the positively charged DMAEMA moieties without changing the behavior of the PDMAEMA chains. At intermediate gold concentration, the ions induce a progressive contraction of the corona's chains and dehydration of micelles. At large gold concentration, the corona becomes a fully dry phase loaded with gold ions, which induces micelle aggregation. Radiolysis of the solution by an intense X-ray beam produces different types of gold nanoparticles with respect to RAuCl4-/DMAEMA and irradiation time. At RAuCl4-/DMAEMA = 0.033, irradiation produces in the first step gold clusters in the micelle corona which in the second step merge to form nanoparticles of a similar size to that of the micelle. Conversely, at RAuCl4-/DMAEMA = 0.33, micelles do not operate as templates but only as nucleation zones and large nanoparticles grow outside the micelles.

Insights into the functional aspects of poly(ADP-ribose) polymerase-1 (PARP-1) in mitochondrial homeostasis in Dictyostelium discoideum.

Poly(ADP-ribose) Polymerase-1 (PARP-1) is predominantly a nuclear protein and involved in various cellular processes like DNA repair, cell death, development, chromatin modulation etc. PARP-1 utilizes NAD+ and adds negatively charged PAR moieties on the target proteins. Over-activation of PARP-1 has been shown to cause energy crisis mediated cell death in which mitochondrial homeostasis is also affected. Moreover, the presence of mitochondrial NAD+ pools highlights the role of PARP-1 in mitochondria. The aim of present study is to understand the physiological role of PARP-1 in regulating mitochondrial functioning by varying the levels of PARP-1 in Dictyostelium discoideum. Intra-mitochondrial PARylation was analyzed by indirect immunofluorescence. Further, the effect of altered levels of PARP-1 i.e. overexpression, downregulation, knockout and its chemical inhibition was studied on mitochondrial respiration, reactive oxygen species (ROS) levels, ATP production, mitochondrial fission-fusion, mitochondrial morphology and mitochondrial DNA (mtDNA) content of D. discoideum. Our results show intra-mitochondrial PARylation under oxidative stress. Altered levels of PARP-1 caused impairment in the mitochondrial respiratory capacity, leading to elevated ROS levels and reduced ATP production. Moreover, PARP-1 affects the mitochondrial morphology and mtDNA content, alters the mitochondrial fission-fusion processes in lieu of preventing cell death under physiological conditions. The current study highlights the physiological role of PARP-1 in mitochondrial respiration, its morphology, fission-fusion processes and mtDNA maintenance in D. discoideum. This study would provide new clues on the PARP-1's crucial role in mitochondrial homeostasis, exploring the therapeutic potential of PARP-1 in various mitochondrial diseases.

A myosin-7B–dependent endocytosis pathway mediates cellular entry of α-synuclein fibrils and polycation-bearing cargos

Cell-to-cell transmission of misfolding-prone α-synuclein (α-Syn) has emerged as a key pathological event in Parkinson's disease. This process is initiated when α-Syn-bearing fibrils enter cells via clathrin-mediated endocytosis, but the underlying mechanisms are unclear. Using a CRISPR-mediated knockout screen, we identify SLC35B2 and myosin-7B (MYO7B) as critical endocytosis regulators for α-Syn preformed fibrils (PFFs). We show that SLC35B2, as a key regulator of heparan sulfate proteoglycan (HSPG) biosynthesis, is essential for recruiting α-Syn PFFs to the cell surface because this process is mediated by interactions between negatively charged sugar moieties of HSPGs and clustered K-T-K motifs in α-Syn PFFs. By contrast, MYO7B regulates α-Syn PFF cell entry by maintaining a plasma membrane-associated actin network that controls membrane dynamics. Without MYO7B or actin filaments, many clathrin-coated pits fail to be severed from the membrane, causing accumulation of large clathrin-containing "scars" on the cell surface. Intriguingly, the requirement for MYO7B in endocytosis is restricted to α-Syn PFFs and other polycation-bearing cargos that enter cells via HSPGs. Thus, our study not only defines regulatory factors for α-Syn PFF endocytosis, but also reveals a previously unknown endocytosis mechanism for HSPG-binding cargos in general, which requires forces generated by MYO7B and actin filaments.

Engineering the surface of prostate tumor cells and hyaluronan/chitosan multilayer films to modulate cell-substrate adhesion properties

This paper explores different film assembly conditions of the polyelectrolyte solutions of hyaluronan (HA) and chitosan (CHI), as well as both substrate and cell surface modifications, to investigate PC3 cells adhesion properties. UV–Visible, AFM-IR and Zeta potential techniques indicate that the solution ionic strength is a relevant parameter to modulate the free carboxylic groups of HA on the film surface. In addition, capacitive coupling measurements suggest that assembly conditions that favor surface charge mobility inhibit cell adhesion due to polymer rearrangements that support non-specific electrostatic interactions of positively charged CHI residues and the negatively charged cell moieties, rather than specific CD44-hyaluronan interactions. Moreover, the PC3 cells treatment with hyaluronidase and anti-CD44 antibody also highlighted the importance of CD44 binding site availability on the tumor cell adhesion properties. Finally, the conjugation of wheat germ agglutinin on the film surface proved to be a suitable strategy to boost the PC3 cell adhesion properties. Our results reveal the remarkable capacity of HA/CHI films to modulate cell-substrate properties, which pave the road for the development of surfaces suitable for several applications based on biosensing.

A robust anionic sulfonated ferrocene derivative for pH-neutral aqueous flow battery

Despite that aqueous organic redox flow batteries (AORFBs) have recently been extensively investigated for low-cost large-scale energy storage, the option for viable catholyte remains limited. This is further constrained by the incompatibility of those positively charged redox species with the cation-exchange membranes. Here, we report an anionic sulfonated ferrocene derivative (Fc-SO3Na) bearing negatively charged moiety to tackle the above issue. The molecule has a solubility of 2.5 ​M in water and reveals remarkable electrochemical reversibility and stability in pH-neutral solution. A flow battery with Fc-SO3Na cathodic redox species and zinc metal as anode demonstrated superb performance in conjunction with sulfonated poly (ether ether ketone)/titanium oxide composite membrane (SPEEK/TiO2) as separator. The cell exhibits a capacity retention of 99.9975% per cycle at low concentration and at high concentration it shows an energy density of 27.1 ​Wh L−1 which is fairly comparable to the VFBs (25–30 ​Wh L−1). The volumetric capacity of catholyte could be further promoted to 293.5 Ah L−1 via redox-targeting reaction when LiFePO4 is loaded into cathodic tank.

Adsorption of nucleotides on clay surfaces: Effects of mineral composition, pH and solution salts

In the context of the origin of life, clays have been proposed as possible materials to adsorb, protect and potentially foster the formation of complex bio molecules. In the present study, the adsorption of nucleotides onto clay surfaces has been tackled through classical molecular dynamics calculations. Various parameters have been varied by modelling the deoxyguanosine mono phosphate molecule at the basal surface of two clay minerals: montmorillonite and nontronite, at pH = 3 and 7, and in a 0.5 M NaCl solution in presence or absence of Ca2+ divalent cations. It has been firstly observed that counter cations in solution adopts a three-layers structure above the mineral basal surfaces which can be modified by the mineral composition, the location of the surface charge, and results in substantial effects on nucleotide adsorption. For montmorillonite, for which the charge is located in the octahedral (inner) layer, the two closest counter cations layers above the mineral surface are less populated while the third layer comprises the largest cations density. For nontronite, for which the negative charge is located on the surface oxygen atoms of the tetrahedral layer in contact with the aqueous solution, the first two counter cations layers are the most populated. The negative charge on the surface is thus screened by the first two layers above nontronite surface, and by only the third layer for montmorillonite. As a result, the negatively charged phosphate moiety of nucleotides can approach closer to the surface of nontronite by coordinating with the first two layers cations and the nucleobase adsorb on the surface in a parallel orientation maximizing Van der Walls interactions. On montmorillonite, the phosphate coordinates the cations of the third layer and thus remains rather far from the surface, which does not allow the nucleobase parallel binding. These theoretical results explain experimental results on the effect of mineral and solution composition on the adsorption of nucleotides on the surface of swelling clays.

New BI and TRI-Thiazole copper (II) complexes in the search of new cytotoxic drugs against breast cancer cells

New thiazolyl derivatives (BT and TT) and their copper (II) complexes [Cu2Cl2(BT)2] (Cu-BT) and [Cu4ClO2(TT)2]PF6⋅3.5H2O (Cu-TT) were synthesized and characterized by elemental analysis, 1H NMR and 13C NMR, HRMS, X-ray diffraction, IR and UV–Vis spectroscopies. The crystal structure of Cu-BT shows the formation of a dinuclear complex where each copper(II) center is bonded to two thiazol N atoms, from different BT ligands, one deprotonated amide N atom, an O atom from the ester terminal groups and a chlorine atom. The structure found for Cu-TT is a positively charged tetranuclear moiety containing two deprotonated TT ligands, a chlorine anion, two hydroxide anions acting as bridges between the copper centers and a water molecule. The cytotoxic activity of both copper complexes was evaluated on metastatic breast cancer cell lines, characterized for its rapidly dividing behavior. Both, Cu-BT and Cu-TT, show higher cytotoxic activity against these tumor cells than free BT and TT and also than cisplatin. In addition, we found that both complexes interact with DNA. Consistently, they also show cytotoxicity against a rapidly dividing non-tumor cell line, although with higher IC50, being such interaction and selectivity an indicator of the possible coexistence of more than one mechanism of action.

Zwitterion and Oligo(ethylene glycol) Synergy Minimizes Nonspecific Binding of Compact Quantum Dots.

Quantum dots (QDs) are a class of fluorescent nanocrystals in development as labels for molecular imaging in cells and tissues. Recently, coatings for quantum dots based on multidentate polymers have improved labeling performance in a range of bioanalytical applications, primarily due to reduced probe hydrodynamic size. Now, an ongoing challenge is to eliminate nonspecific binding between these small probes and cellular components that mask specifically labeled molecules. Here, we describe insights into controlling and minimizing intermolecular interactions governing nonspecific binding using multidentate polymers with tunable hydrophilic functional groups that are cationic, anionic, zwitterionic (ZW), or nonionic (oligoethylene glycol; OEG). By fixing surface-binding groups and polymer length, coated colloids have similar sizes but diverse physicochemical properties. We measure binding to globular proteins, fixed cells, and living cells and observe a substantial improvement in nonspecific binding resistance when surfaces are functionalized with a combination of ZW and OEG. The independent underlying effects of counterion adsorption and flexibility appear to synergistically resist adsorption when combined, particularly for fixed cells enriched in both charged and hydrophobic moieties. We further show that ZW-OEG QDs are stable under diverse conditions and can be self-assembled with antibodies to specifically label surface antigens on living cells and cytoplasmic proteins in fixed cells. This surface engineering strategy can be adopted across the diverse range of colloidal materials currently in use and in development for biomedical applications to optimize their molecular labeling specificity.

Host-Guest Complexation of Monoanionic and Dianionic Guests with a Polycationic Pillararene Host: Same Two-Step Mechanism but Striking Difference in Rate upon Inclusion.

Supramolecular dynamic studies provide the most direct information to elucidate the binding mechanisms of the systems and yet are underdeveloped in pillararene chemistry. Herein, we describe the first real-time study on the binding dynamics of a water-soluble per-substituted pillar[5]arene (H1) with pentanesulfonate (G1) and butane-1,4-disulfonate (G2). Both the host-guest complexes were formed via a two-step process. The first step, equilibrated within 1 ms for both guests, was associated with the formation of a 1:1 exclusion complex, and the second step was the conversion of this exclusion complex to the inclusion complex. Threading and dethreading processes in the second step for G2 were at least a million times slower than for G1. Kinetics results reveal that for H1, complexation with a charged guest may follow the same "two-step" mechanism regardless of the number of charged moieties in the guests and the rate of the complexation. This study may advance the mechanistic understanding necessary for further development of functional supramolecular systems.

Capacitive Deionization of Divalent Cations for Water Softening Using Functionalized Carbon Electrodes.

Water softening is a relatively untapped area of research in capacitive deionization (CDI). In this work, we demonstrate how an asymmetric combination of oxidized and aminated carbon can be used for selective removal of divalent cations for water softening. We first show how higher electrosorption performances can be achieved in single-salt experiments involving NaCl, KCl, MgCl2, and CaCl2 before proceeding to multi-salt experiments using different combinations of the four salts. The salt combinations are chosen to investigate one of the three factors: (1) ionic mass, (2) ionic charge, or (3) concentration. We show how divalent selectivity can be achieved due to high local electrostatic attraction between negatively charged oxygen moieties and divalent cations. Additionally, an ion-exchange process between the oxidized carbon surface and cations can result in lower pH values, which prevent the precipitation of scale-forming ions.

Poly(peptide): Synthesis, Structure, and Function of Peptide-Polymer Amphiphiles and Protein-like Polymers.

In this Account, we describe the organization of functional peptides as densely arrayed side chains on polymer scaffolds which we introduce as a new class of material called poly(peptide). We describe two general classes of poly(peptide): (1) Peptide-Polymer Amphiphiles (PPAs), which consist of block copolymers with a dense grouping of peptides arrayed as the side chains of the hydrophilic block and connected to a hydrophobic block that drives micelle assembly, and (2) Protein-like Polymers (PLPs), wherein peptide-brush polymers are composed from monomers, each containing a peptide side chain. Peptides organized in this manner imbue polymers or polymeric nanoparticles with a range of functional qualities inherent to their specific sequence. Therefore, polymers or nanoparticles otherwise lacking bioactivity or responsiveness to stimuli, once linked to a peptide of choice, can now bind proteins, enter cells and tissues, have controlled and switchable biodistribution patterns, and be enzyme substrates (e.g., for kinases, phosphatases, proteases). Indeed, where peptide substrates are incorporated, kinetically or thermodynamically driven morphological transitions can be enzymatically induced in the polymeric material. Synergistically, the polymer enforces changes in peptide activity and function by virtue of packing and constraining the peptide. The scaffold can protect peptides from proteolysis, change the pharmacokinetic profile of an intravenously injected peptide, increase the cellular uptake of an otherwise cell impermeable therapeutic peptide, or change peptide substrate activity entirely. Moreover, in addition to the sequence-controlled peptides (generated by solid phase synthesis), the polymer can carry its own sequence-dependent information, especially through living polymerization strategies allowing well-defined blocks and terminal labels (e.g., dyes, contrast agents, charged moieties). Hence, the two elements, peptide and polymer, cooperate to yield materials with unique function and properties quite apart from each alone. Herein, we describe the development of synthetic strategies for accessing these classes of biomolecule polymer conjugates. We discuss the utility of poly(peptide)-based materials in a range of biomedical applications, including imaging of diseased tissues (myocardial infarction and cancer), delivering small molecule drugs to tumors with high specificity, imparting cell permeability to otherwise impermeable peptides, protecting bioactive peptides from proteolysis in harsh conditions (e.g., stomach acid and whole blood), and transporting proteins into traditionally difficult-to-transfect cell types, including stem cells. Poly(peptide) materials offer new properties to both the constituent peptides and to the polymers, which can be tuned by the design of the oligopeptide sequence, degree of polymerization, peptide arrangement on the polymer backbone, and polymer backbone chemistry. These properties establish this approach as valuable for the development of peptides as medicines and materials in a range of settings.