The Surfactant Properties of Clindamycin as a Useful Adjunct for Removing Ruptured Silicone Implants.

Background: Silicone gel removal after breast implant rupture is a difficult task. Silicone is hydrophobic and thus cannot be irrigated effectively with saline. Attempts at mechanical removal with sponges are often partially successful.

Switchable Coacervate Formation via Amino Acid Functionalization of Poly(dehydroalanine).

Our group recently developed a family of side-chain amino acid-functionalized poly(S-alkyl-l-homocysteines), (Xaa = generic amino acid), which possess the ability to form environmentally responsive coacervates in water. In an effort to further study how the molecular structure affects polypeptide coacervate formation, we prepared side-chain amino acid-functionalized poly(S-alkyl--cysteines), , via post-polymerization modification of poly(dehydroalanine), . The use of the platform allowed straightforward synthesis of a diverse range of side-chain amino acid-functionalized polypeptides via direct reaction of unprotected l-amino acid 2-mercaptoethylamides with .

Sulfur Switches for Responsive Peptide Materials.

There is considerable recent interest in the synthesis and development of peptide-based materials as mimics of natural biological assemblies that utilize proteins and peptides to form organized structures and develop beneficial properties. Due to their potential compatibility with living organisms, synthetic peptide materials are also being developed for applications such as cell grafting, therapeutic delivery, and implantable diagnostic devices. One desirable feature for such applications is the ability to design materials that can respond to stimuli by changes in their structure or properties under biologically relevant conditions.

Preparation and stability of pegylated poly(S-alkyl-L-homocysteine) coacervate core micelles in aqueous media.

We report development and preparation of synthetic polypeptide based, coacervate core polyelectrolyte complex micelles, PCMs, in aqueous media, which were characterized and evaluated for the encapsulation and in vitro release of a model single-stranded RNA, polyadenylic acid, poly(A). Cationic, α-helical polypeptides pegylated at their N-termini, PEG-b-5b and PEG-b-5c were designed to form coacervate core PCMs upon mixing with multivalent anions in aqueous media. Sodium tripolyphosphate (TPP) and poly(A) were used as model multivalent anions that allowed optimization of polypeptide composition and chain length for formation of stable, nanoscale PCMs.

Controlled Synthesis and Properties of Poly(l-homoserine).

We report the preparation of a new water-soluble, nonionic homopolypeptide poly(l-homoserine) as well as poly(l-homoserine) block copolymers with controllable segment lengths. The conformational preferences of poly(l-homoserine) were also determined in both the solid state and in solution. Poly(l-homoserine) is soluble in water and adopts a disordered conformation that makes it a promising addition to the small class of nonionic, water-soluble homopolypeptides with potential for development for applications in biology.

Poly(dehydroalanine): Synthesis, Properties, and Functional Diversification of a Fluorescent Polypeptide.

Via the design of a new, soluble poly(-alkyl-l-cysteine) precursor, a route was developed for the successful preparation of long-chain poly(dehydroalanine), , as well as the incorporation of dehydroalanine residues and segments into copolypeptides. Based on experimental and computational data, was found to adopt a previously unobserved "hybrid coil" structure, which combines the elements of 2-helical and 3-helical conformations. Analysis of the spectroscopic properties of revealed that it possesses a strong inherent blue fluorescence, which may be amenable for use in imaging applications.

Active Controlled and Tunable Coacervation Using Side-Chain Functional α-Helical Homopolypeptides.

We report the development of new side-chain amino acid-functionalized α-helical homopolypeptides that reversibly form coacervate phases in aqueous media. The designed multifunctional nature of the side-chains was found to provide a means to actively control coacervation via mild, biomimetic redox chemistry as well as allow response to physiologically relevant environmental changes in pH, temperature, and counterions. These homopolypeptides were found to possess properties that mimic many of those observed in natural coacervate forming intrinsically disordered proteins.

Injectable diblock copolypeptide hydrogel provides platform to deliver effective concentrations of paclitaxel to an intracranial xenograft model of glioblastoma.

Introduction: Surgical resection and systemic chemotherapy with temozolomide remain the mainstay for treatment of glioblastoma. However, many patients are not candidates for surgical resection given inaccessible tumor location or poor health status. Furthermore, despite being first line treatment, temozolomide has only limited efficacy.

Overview of Host Defense Peptides and Their Applications for Plastic and Reconstructive Surgeons.

Background: Host defense peptides are a family of endogenous short peptides that are found in all living beings and play a critical role in innate immunity against infection.

Methods: A nonsystematic review of host defense peptides was conducted with specific interest in properties and applications relevant to plastic and reconstructive surgery.

Results: In addition to their direct antimicrobial actions against pathogens, including multidrug-resistant bacteria, they also demonstrate important functions in immunomodulation, tumor cell lysis, and tissue regeneration.

Design of Thermoresponsive Elastin-Like Glycopolypeptides for Selective Lectin Binding and Sorting.

Selective lectin binding and sorting was achieved using thermosensitive glycoconjugates derived from recombinant elastin-like polypeptides (ELPs) in simple centrifugation-precipitation assays. A recombinant ELP, (VPGXG), containing periodically spaced methionine residues was used to enable chemoselective postsynthetic modification via thioether alkylation using alkyne functional epoxide derivatives. The resulting sulfonium groups were selectively demethylated to give alkyne functionalized homocysteine residues, which were then reacted with azido-functionalized monosaccharides to obtain ELP glycoconjugates with periodic saccharide functionality.

Self-Sorting Microscale Compartmentalized Block Copolypeptide Hydrogels.

Multicomponent interpenetrating network hydrogels possessing enhanced mechanical stiffness compared to their individual components were prepared via physical mixing of diblock copolypeptides that assemble by either hydrophobic association or polyion complexation in aqueous media. Optical microscopy analysis of fluorescent-probe-labeled multicomponent hydrogels revealed that the diblock copolypeptide components rapidly and spontaneously self-sort to form distinct hydrogel networks that interpenetrate at micron length scales. These materials represent a class of microscale compartmentalized hydrogels composed of degradable, cell-compatible components, which possess rapid self-healing properties and independently tunable domains for downstream applications in biology and additive manufacturing.

Tunable, Functional Diblock Copolypeptide Hydrogels Based on Methionine Homologs.

The preparation of new diblock copolypeptide hydrogels derived from homologs of l-methionine, that is, l-homomethionine and l-6-(methylthio)-l-norleucine is described. Compared to l-methionine residues, use of l-methionine homologs allow improved copolymerization with l-leucine residues to give well-defined block copolypeptides. These copolypeptides are subsequently modified using robust thioether alkylation reactions employing a variety of functional epoxides, which yield samples capable of forming transparent, self-healing hydrogels in water.

Modification of Poly(5,6-epoxy-l-norleucine) Gives Functional Polypeptides with Alternative Side-Chain Linkages.

The preparation and characterization of a new epoxide containing polypeptide, poly(5,6-epoxy-l-norleucine), via postpolymerization modification of poly(l-homoallylglycine) is described. Addition of thiols to the epoxide groups in poly(5,6-epoxy-l-norleucine) was studied as a means to prepare side-chain functional polypeptides. The solution properties of the derivatized polypeptides were studied in water and compared to similar thioether containing functional polypeptides prepared via different routes.

Influence of Sulfoxide Group Placement on Polypeptide Conformational Stability.

The synthesis of a homologous series containing five new nonionic sulfoxide containing polypeptides was described. Sulfoxide groups bestowed water solubility for all homologues, which allowed their use as a model for study of helix-coil transitions in water while avoiding contributions from charged groups or phase separation. Polypeptides were found to adopt chain conformations in water that were dependent on distance of sulfoxides from chain backbones, overall side-chain lengths, and solvent.

Human Vault Nanoparticle Targeted Delivery of Antiretroviral Drugs to Inhibit Human Immunodeficiency Virus Type 1 Infection.

"Vaults" are ubiquitously expressed endogenous ribonucleoprotein nanoparticles with potential utility for targeted drug delivery. Here, we show that recombinant human vault nanoparticles are readily engulfed by certain key human peripheral blood mononuclear cells (PBMC), predominately dendritic cells, monocytes/macrophages, and activated T cells. As these cell types are the primary targets for human immunodeficiency virus type 1 (HIV-1) infection, we examined the utility of recombinant human vaults for targeted delivery of antiretroviral drugs.

Self-Healing Multiblock Copolypeptide Hydrogels via Polyion Complexation.

Diblock, triblock, and pentablock copolypeptides were designed and prepared for formation of polyion complex hydrogels in aqueous media. Increasing the number of block segments was found to allow formation of hydrogels with substantially enhanced stiffness at equivalent concentrations. Use of similar length ionic segments also allowed mixing of different block architectures to fine-tune hydrogel properties.

Versatile N-Methylaminooxy-Functionalized Polypeptides for Preparation of Neoglycoconjugates.

The preparation and characterization of a new set of well-defined polypeptides containing N-methylaminooxy side-chain functionality is described. These functional groups enabled the direct coupling of polypeptides with a variety of unmodified reducing saccharides in water to give neoglycopolypeptides in high yields. The use of different polypeptide scaffolds resulted in neoglycoconjugates with tunable chain conformations, hydrophobicity, and charge.

Influence of Sulfur-Containing Diamino Acid Structure on Covalently Crosslinked Copolypeptide Hydrogels.

Biologically occurring non-canonical di-α-amino acids were converted into new di-N-carboxyanhydride (di-NCA) monomers in reasonable yields with high purity. Five different di-NCAs were separately copolymerized with tert-butyl-l-glutamate NCA to obtain covalently crosslinked copolypeptides capable of forming hydrogels with varying crosslinker density. Comparison of hydrogel properties with residue structure revealed that different di-α-amino acids were not equivalent in crosslink formation.

Required growth facilitators propel axon regeneration across complete spinal cord injury.

Transected axons fail to regrow across anatomically complete spinal cord injuries (SCI) in adults. Diverse molecules can partially facilitate or attenuate axon growth during development or after injury, but efficient reversal of this regrowth failure remains elusive. Here we show that three factors that are essential for axon growth during development but are attenuated or lacking in adults-(i) neuron intrinsic growth capacity, (ii) growth-supportive substrate and (iii) chemoattraction-are all individually required and, in combination, are sufficient to stimulate robust axon regrowth across anatomically complete SCI lesions in adult rodents.

Homoallylglycine residues are superior precursors to orthogonally modified thioether containing polypeptides.

Homoallylglycine N-carboxyanhydride, Hag NCA, monomers were synthesized and used to prepare polypeptides containing Hag segments with controllable lengths of up to 245 repeats. Poly(l-homoallylglycine), GHA, was found to adopt an α-helical conformation, which provided good solubility in organic solvents and allowed high yield functionalization of its alkene side-chains via radical promoted addition of thiols. The conformations of these derivatives were shown to be switchable between α-helical and disordered states in aqueous media using thioether alkylation or oxidation reactions.