Skip to main content
eScholarship
Open Access Publications from the University of California

Scholarly Works (6 results)

  • Article
  • Peer Reviewed
UCLA Previously Published Works (2014)
We report the design and synthesis of poly(S-alkyl-L-homocysteine)s, which were found to be a new class of readily prepared, multiresponsive polymers that possess the unprecedented ability to respond in different ways to different stimuli, either through a change in chain conformation or in water solubility. The responsive properties of these materials are also effected under mild conditions and are completely reversible for all pathways. The key components of these polymers are the incorporation of water solubilizing alkyl functional groups that are integrated with precisely positioned, multiresponsive thioether linkages. This promising system allows multimodal switching of polypeptide properties to obtain desirable features, such as coupled responses to multiple external inputs.
    Cover page: Multimodal Switching of Conformation and Solubility in Homocysteine Derived Polypeptides
    • Thesis
    • Peer Reviewed
    UCLA Electronic Theses and Dissertations (2012)

    Synthetic polypeptides have shown great promise as materials for biotechnology and medicine, with applications in tissue engineering, drug delivery, and as therapeutics. Despite significant advances in the preparation of well-defined polypeptides and the development of self-assembling materials, a need remains for a broader scope of polypeptides with functionalities that mimic the complexity and function of post-translationally modified natural proteins. The display of functionalities that have therapeutic effects, target materials to specific tissues, passivate the immune response, or have stimuli responsive behavior, are highly desirable yet generally require complex and inefficient synthetic approaches.

    This dissertation reports several distinct advances in the preparation of a wide variety of highly functional polypeptide materials. Progress in both the polymerization of functionalized NCA monomers and the post-polymerization modification of polypeptides is described. A new method of NCA purification was developed, and has allowed access to diverse monomers with functionalities previously unattainable due to impurities that impeded polymerization. This purification technique was applied to the synthesis of glycosylated NCAs, which yielded the first living polymerizations of glycosylated NCAs and gave access to glycopolypeptides with unique properties and conformations. The display of sugar functionalities from synthetic polymers is an area of great interest due to the many attractive properties imparted upon the parent material, such as non-ionic water solubility, biological targeting, and shielding of the polypeptide from proteases. These glycopolypeptides were used to explore the effect of conformation on self-assembly and ligand binding, and to develop vesicles with potential medical applications in targeted drug delivery. In addition, a new conjugation technique for facile post-polymerization modification of polypeptides is described. This conjugation utilizes the unique chemistry of the natural amino acid methionine to allow chemoselective introduction of a wide variety of functional groups via alkylation. We investigated the stability of various alkylated methionines to thiolysis, and developed a simple method to attach and later remove different groups. Finally, work performed during an NSF-IGERT funded internship at HRL Laboratories Inc. is described. Surface modification of carbon foam anodes for microbial fuel cell applications was explored, and the use of thermogravimetric analysis as technique to evaluate biofilm formation was developed.

      Cover page: Functional Polypeptides for Biomedical Applications
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2014)
      Glycosylated peptides and proteins are ubiquitous in nature and display a wide range of biological functions including mediation of recognition events, protection from proteases, and lubrication in eyes and joints. Similarly, synthetic glycopolypeptides are also expected to show great potential as biomedical materials (e.g. scaffolds for tissue repair and drug carriers), as well as serve as valuable tools for probing carbohydrate-protein interactions. Although block copolypeptides and other complex polypeptide architectures have been known for some time, the synthesis of complex and well-defined glycopolypeptide materials, until recently, has been challenging. This article reviews the many advances and accomplishments made in the past few years toward development of strategies and methods for the preparation of synthetic glycopolypeptides via ring opening polymerization. © 2014 The Royal Society of Chemistry.
        Cover page: Recent advances in glycopolypeptide synthesis
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2013)
        We have developed a facile, scalable method for preparation of enzyme-responsive copolypeptide vesicles that requires no protecting groups or expensive components. We designed amphiphilic copolypeptides containing segments of water-soluble methionine sulfoxide, M(O), residues that were prepared by synthesis of a fully hydrophobic precursor diblock copolypeptide, poly(l-methionine)65-b-poly(L-leucine0.5-stat-L-phenylalanine0.5)20, M65(L0.5/F0.5)20, followed by its direct oxidation in water to give the amphiphilic M(O) derivative, M(O)65(L0.5/F0.5)20. Assembly of M(O)65(L0.5/F0.5)20 in water gave vesicles with average diameters of a few micrometers that could then be extruded to nanoscale diameters. The M(O) segments in the vesicles were found to be substrates for reductase enzymes, which regenerated hydrophobic M segments and resulted in a change in supramolecular morphology that caused vesicle disruption and release of cargos.
          Cover page: Enzyme-Triggered Cargo Release from Methionine Sulfoxide Containing Copolypeptide Vesicles
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2015)
          Cell penetrating peptides (CPPs) are intriguing molecules that have received much attention, both in terms of mechanistic analysis and as transporters for intracellular therapeutic delivery. Most CPPs contain an abundance of cationic charged residues, typically arginine, where the amino acid compositions, rather than specific sequences, tend to determine their ability to enter cells. Hydrophobic residues are often added to cationic sequences to create efficient CPPs, but typically at the penalty of increased cytotoxicity. Here, we examined polypeptides containing glycosylated, cationic derivatives of methionine, where we found these hydrophilic polypeptides to be surprisingly effective as CPPs and to also possess low cytotoxicity. X-ray analysis of how these new polypeptides interact with lipid membranes revealed that the incorporation of sterically demanding hydrophilic cationic groups in polypeptides is an unprecedented new concept for design of potent CPPs.
            Cover page: Reinventing Cell Penetrating Peptides Using Glycosylated Methionine Sulfonium Ion Sequences
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2015)
            Tuning the lower critical solution temperature (LCST) of temperature-responsive recombinant elastin-like polypeptides has usually been achieved by designing different protein sequences, in terms of amino acid composition and length, implying tedious molecular cloning steps. In the present work, we have explored the chemoselective alkylation of methionine as an easy means to modify elastin repeat side chains and easily modulate the LCST of the polypeptides. Such a versatile synthetic method shall practically be exploited to modulate any properties of recombinant polymers.
              Cover page: Quantitative Side-Chain Modifications of Methionine-Containing Elastin-Like Polypeptides as a Versatile Tool to Tune Their Properties
              Top