Neoglycolipids for Prolonging the Effects of Peptides: Self-Assembling Glucagon-like Peptide 1 Analogues with Albumin Binding Properties and Potent in Vivo Efficacy
Research output: Contribution to journal › Journal article › Research › peer-review
Novel principles for optimizing the properties of peptide-based drugs are needed in order to leverage their full pharmacological potential. We present the design, synthesis, and evaluation of a library of neoglycolipidated glucagon-like peptide 1 (GLP-1) analogues, which are valuable drug candidates for treatment of type 2 diabetes and obesity. Neoglycolipidation of GLP-1 balanced the lipophilicity, directed formation of soluble oligomers, and mediated albumin binding. Moreover, neoglycolipidation did not compromise bioactivity, as in vitro potency of neoglycolipidated GLP-1 analogues was maintained or even improved compared to native GLP-1. This translated into pronounced in vivo efficacy in terms of both decreased acute food intake and improved glucose homeostasis in mice. Thus, we propose neoglycolipidation as a novel, general method for modulating the properties of therapeutic peptides
Original language | English |
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Journal | Molecular Pharmaceutics |
Volume | 14 |
Issue number | 1 |
Pages (from-to) | 193-205 |
Number of pages | 13 |
ISSN | 1543-8384 |
DOIs | |
Publication status | Published - 2017 |
- neoglycolipid, lipidation, glucagon-like peptide 1, glycolipid, half-life extension, biopharmaceutical, peptide
Research areas
ID: 176369858