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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. Insulin-like peptide secretion is mediated by peroxisome-Golgi interplay

   https://doi.org/10.1101/2025.05.26.656179  

   König, Marie A; Kucharowski, Nicole; Dancourt_Ramos, Darla P; Soyka, Hannah; Wunderling, Klaus; Bülow, Torsten R; Yaghmour, Mohamed H; Thiele, Christoph; Ache, Jan M; Kuerschner, Lars; et al (May 2025, bioRxiv)

   Abstract Insulin is a peptide hormone that is secreted in Golgi-derived dense-core vesicles from mammalian pancreatic beta-cells in response to nutrients. InDrosophila melanogaster, three insulin-like peptides are secreted as neuropeptides from the insulin-producing cells in the brain. Peroxisomes are lipid-metabolizing organelles that engage into various membrane contact sites with other organelles. Impaired peroxisomal metabolism has been associated with beta-cell apoptosis and impaired insulin secretion. How peroxisomes contribute to insulin and neuropeptide secretion is unknown. Here we demonstrate that peroxisomes interact with the Golgi apparatus inDrosophilainsulin-producing cells. Secretion of insulin-like peptide 2 is cell-intrinsically impaired in mutants lacking the peroxisome assembly factor Pex19. Loss of peroxisomes shifts the profile of sphingolipids towards longer sphingoid bases and leads to accumulation of sphingolipids in the Golgi. We show that peroxisomes dynamically interact with the Golgi in insulin-producing cells and that Pex19 directly contributes to peroxisome-Golgi interaction via the fatty acyl-CoA reductase FAR2/waterproof in the peroxisomal membrane. We propose that this peroxisome-Pex19-Golgi axis is required to adjust Golgi membranes upon starvation by withdrawing lipids with longer side chains, thereby optimizing Golgi membrane flexibility for dense-core vesicle secretion upon refeeding. 

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3. Zwitterionic Polymer Conjugated Glucagon-like Peptide-1 for Prolonged Glycemic Control

   https://doi.org/10.1021/acs.bioconjchem.0c00286  

   Tsao, Caroline; Zhang, Peng; Yuan, Zhefan; Dong, Dianyu; Wu, Kan; Niu, Liqian; McMullen, Patrick; Luozhong, Sijin; Hung, Hsiang-Chieh; Cheng, Yu-Hong; et al (July 2020, Bioconjugate Chemistry)
4. A free‐energy landscape for the glucagon‐like peptide 1 receptor GLP1R

   https://doi.org/10.1002/prot.25777  

   Alhadeff, Raphael; Warshel, Arieh (August 2019, Proteins: Structure, Function, and Bioinformatics)

   Abstract G‐protein‐coupled receptors (GPCRs) are among the most important receptors in human physiology and pathology. They serve as master regulators of numerous key processes and are involved in as well as cause debilitating diseases. Consequently, GPCRs are among the most attractive targets for drug design and pharmaceutical interventions (>30% of drugs on the market). The glucagon‐like peptide 1 (GLP‐1) hormone receptor GLP1R is closely involved in insulin secretion by pancreatic β‐cells and constitutes a major druggable target for the development of anti‐diabetes and obesity agents. GLP1R structure was recently solved, with ligands, allosteric modulators and as part of a complex with its cognate G protein. However, the translation of this structural data into structure/function understanding remains limited. The current study functionally characterizes GLP1R with special emphasis on ligand and cellular partner binding interactions and presents a free‐energy landscape as well as a functional model of the activation cycle of GLP1R. Our results should facilitate a deeper understanding of the molecular mechanism underlying GLP1R activation, forming a basis for improved development of targeted therapeutics for diabetes and related disorders. 

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5. Novel HIV-1 fusion peptide immunogens using glycan-engineered alphavirus-like particles

   https://doi.org/10.1101/2025.05.02.651772  

   Oh, Seo-Ho; Gudipati, Dedeepya R; Shi, Wei; Zhao, Peng; Wu, Winston; Boyington, Jeffrey C; Nariya, Hardik K; McGhee, Emily G; Azzam, Tala; Raghunathan, Vedhika; et al (May 2025, bioRxiv)

   Summary Immunofocusing on conserved, subdominant epitopes is critical for vaccines against highly diverse viruses such as HIV-1, influenza, and SARS-CoV-2. The eight-residue N-terminus of the HIV-1 fusion peptide (FP) is one such example of a promising yet small target. We developed new FP immunogens using three alphavirus-like particles (VLPs) and introduced additional glycans to mask shared carrier-specific epitopes. In two independent guinea pig studies, sequential immunization with heterologous carriers enhanced FP-directed antibody titers, which were further improved with glycan engineering. Separately, using diverse FP variants sharing the same N-terminal six amino acids increased neutralizing antibody titers. When combined, these two strategies led to higher FP-directed titers and, after Env trimer boosting, induced FP-directed neutralizing antibodies against multi-clade wild-type HIV-1 in nearly all animals. These findings established the importance of minimizing recurrent off-target epitopes across immunizations and support the engineered VLPs as a promising platform for peptide immunization. HighlightsNovel HIV-1 fusion peptide immunogens using glycan-engineered alphavirus-like particlesImproved FP-directed response by minimizing recurrent carrier-specific epitopes across immunizationsImproved neutralizing response by sequential immunization with diverse FP variantsFP-directed antibodies neutralizing multi-clade wildtype viruses in nearly all animals 

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