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1. Effect of Peptide Sequence on the LCST-Like Transition of Elastin-Like Peptides and Elastin-Like Peptide–Collagen-Like Peptide Conjugates: Simulations and Experiments

   https://doi.org/10.1021/acs.biomac.8b01503  

   Prhashanna, Ammu ; Taylor, Phillip A. ; Qin, Jingya ; Kiick, Kristi L. ; Jayaraman, Arthi ( January 2019 , Biomacromolecules)
2. Manipulation of the dually thermoresponsive behavior of peptide‐based vesicles through modification of collagen‐like peptide domains

   https://doi.org/10.1002/btm2.10145  

   Dunshee, Lucas C. ; Sullivan, Millicent O. ; Kiick, Kristi L. ( October 2019 , Bioengineering & Translational Medicine)

   Materials that respond to temporally defined exogenous cues continue to be an active pursuit of research toward on‐demand nanoparticle drug delivery applications, and using one or more exogenous temperature stimuli could significantly expand the application of nanoparticle‐based drug delivery formulations under both hyperthermal and hypothermal conditions. Previously we have reported the development of a biocompatible and thermoresponsive elastin‐b‐collagen‐like polypeptide (ELP‐CLP) conjugate that is capable of self‐assembling into vesicles and encapsulating small molecule therapeutics that can be delivered at different rates via a single temperature stimulus. Herein we report the evaluation of multiple ELP‐CLP conjugates, demonstrating that the inverse transition temperature (T_t) of the ELP‐CLPs can be manipulated by modifying the melting temperature (T_m) of the CLP domain, and that the overall hydrophilicity of the ELP‐CLP conjugate also may alter theT_t. Based on these design parameters, we demonstrate that the ELP‐CLP sequence (VPGFG)₆‐(GPO)₇GG can self‐assemble into stable vesicles at 25°C and dissociate at elevated temperatures by means of the unfolding of the CLP domain above itsT_m. We also demonstrate here for the first time the ability of this ELP‐CLP vesicle to dissociate via a hypothermic temperature stimulus by means of exploiting the inverse transition temperature (T_t) phenomena found in ELPs. The development of design rules for manipulating the thermal properties of these bioconjugates will enable future modifications to either the ELP or CLP sequences to more finely tune the transitions of the conjugates for specific biomedical applications.

    

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3. Cationic peptide carriers enable long-term delivery of insulin-like growth factor-1 to suppress osteoarthritis-induced matrix degradation

   https://doi.org/10.1186/s13075-022-02855-1  

   Vedadghavami, Armin ; Hakim, Bill ; He, Tengfei ; Bajpayee, Ambika G. ( December 2022 , Arthritis Research & Therapy)

   Abstract Background Insulin-like growth factor-1 (IGF-1) has the potential to be used for osteoarthritis (OA) treatment but has not been evaluated in clinics yet owing to toxicity concerns. It suffers from short intra-joint residence time and a lack of cartilage targeting following its intra-articular administration. Here, we synthesize an electrically charged cationic formulation of IGF-1 by using a short-length arginine-rich, hydrophilic cationic peptide carrier (CPC) with a net charge of +14, designed for rapid and high uptake and retention in both healthy and arthritic cartilage. Methods IGF-1 was conjugated to CPC by using a site-specific sulfhydryl reaction via a bifunctional linker. Intra-cartilage depth of penetration and retention of CPC-IGF-1 was compared with the unmodified IGF-1. The therapeutic effectiveness of a single dose of CPC-IGF-1 was compared with free IGF-1 in an IL-1α-challenged cartilage explant culture post-traumatic OA model. Results CPC-IGF-1 rapidly penetrated through the full thickness of cartilage creating a drug depot owing to electrostatic interactions with negatively charged aggrecan-glycosaminoglycans (GAGs). CPC-IGF-1 remained bound within the tissue while unmodified IGF-1 cleared out. Treatment with a single dose of CPC-IGF-1 effectively suppressed IL-1α-induced GAG loss and nitrite release and rescued cell metabolism and viability throughout the 16-day culture period, while free IGF at the equivalent dose was not effective. Conclusions CPC-mediated depot delivery of IGF-1 protected cartilage by suppressing cytokine-induced catabolism with only a single dose. CPC is a versatile cationic motif that can be used for intra-cartilage delivery of other similar-sized drugs. 

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4. The role of glucagon-like peptide-1 (GLP-1) in fluid and food intakes in vasopressin-deficient Brattleboro rats

   https://doi.org/10.1016/j.physbeh.2023.114093  

   Brakey, Destiny J. ; Schatz, Kelcie C. ; Paul, Matthew J. ; Daniels, Derek ( April 2023 , Physiology & Behavior)
5. Engineering a Virus-like Particle to Display Peptide Insertions Using an Apparent Fitness Landscape

   https://doi.org/10.1021/acs.biomac.0c00987  

   Robinson, Stephanie A. ; Hartman, Emily C. ; Ikwuagwu, Bon C. ; Francis, Matthew B. ; Tullman-Ercek, Danielle ( October 2020 , Biomacromolecules)